NCT02924727

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of LCZ696 titrated to a target dose of 200 mg twice daily, compared to ramipril titrated to a target dose of 5 mg twice daily.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
5,669

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Dec 2016

Typical duration for phase_3

Geographic Reach
40 countries

479 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 4, 2016

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 5, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

December 9, 2016

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 26, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 26, 2021

Completed
2.3 years until next milestone

Results Posted

Study results publicly available

June 22, 2023

Completed
Last Updated

June 22, 2023

Status Verified

June 1, 2023

Enrollment Period

4.2 years

First QC Date

October 4, 2016

Results QC Date

January 20, 2022

Last Update Submit

June 16, 2023

Conditions

Keywords

Spontaneous AMIHF hospitalizationoutpatient HFLV systolic dysfunctionpulmonary congestionSTEMINSTEMIrandomized clinical trialLCZ696ramipril

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With First CEC (Clinical Endpoint Committee) Confirmed Primary Composite Endpoint

    A confirmed composite endpoint includes cardiovascular (CV) death, heart failure (HF) hospitalization, or outpatient heart failure

    From randomization to first occurrence (up to approximately 43 months)

Secondary Outcomes (5)

  • Number of Participants With a Confirmed Composite of CV Death or HF Hospitalization

    Time from randomization to first occurrence (up to approximately 43 months)

  • Number of Participants With a Confirmed Composite of HF Hospitalization or Outpatient HF

    Time from randomization to first occurrence (approximately up to 43 months)

  • Number of Participants With a Confirmed Composite of CV Death, Non-fatal Spontaneous Myocardial Infarction or Non-fatal Stroke

    Time from randomization to first occurrence (approximately up to 43 months)

  • Total Number of Confirmed Composite Endpoints

    Time from randomization to end of study (approximately up to 43 months)

  • All-cause Mortality for Full Analysis Set (FAS)

    Time from randomization to death (approximately up to 43 months)

Study Arms (2)

LCZ696 (sacubitril/valsartan)

EXPERIMENTAL

Following randomization, patients will receive LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients will be required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors receiving the last dose of that agent during the last 36 hours prior to randomization will receive a valsartan bridge for one day. These patients will receive two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.

Drug: LCZ696 (sacubitril/valsartan)Drug: Placebo of ramiprilDrug: Valsartan

Ramipril

ACTIVE COMPARATOR

Following randomization, patients will receive the Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients will be required to take a total of two pills, (one capsule from the ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to ramipril who were previously treated with ACE inhibitors receiving the last dose of that agent during the last 36 hours prior to randomization will immediately start on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients will receive two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.

Drug: RamiprilDrug: Placebo of LCZ696Drug: Placebo of valsartan

Interventions

LCZ696 (sacubitril/valsartan) tablet will be available in 24/26 mg, 49/51 mg and 97/103 mg, respectively

LCZ696 (sacubitril/valsartan)

Ramipril 1.25 mg, 2.5 mg, and 5 mg oral capsules

Ramipril

Matching placebo of LCZ696 tablets

Ramipril

Matching placebo of ramipril capsule

LCZ696 (sacubitril/valsartan)

Valsartan (VAL489) 40 mg and 80 mg tablets, two doses for 1 day to patients who were previously treated with ACE inhibitors receiving the last dose of that agent during the last 36 hours prior to randomization

LCZ696 (sacubitril/valsartan)

matching placebo of valsartan for one day to patients who will be randomized to received ramipril

Ramipril

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patients ≥ 18 years of age.
  • Diagnosis of spontaneous AMI based on the universal MI definition\* with randomization to occur between 12 hours and 7 days after index event presentation. (\*patients with spontaneous MI event determined to be secondary to another medical condition such as anemia, hypotension, or arrhythmia OR thought to be caused by coronary vasospasm with document normal coronary arteries are not eligible; patients with clinical presentation thought to be related to Takotsubo cardiomyopathy are also not eligible)
  • Evidence of LV systolic dysfunction and/or pulmonary congestion requiring intravenous treatment associated with the index MI event defined as:
  • LVEF ≤40% after index MI presentation and prior to randomization and/or
  • Pulmonary congestion requiring intravenous treatment with diuretics, vasodilators, vasopressors and/or inotropes, during the index hospitalization
  • At least one of the following 8 risk factors:
  • Age ≥ 70 years
  • eGFR \<60 mL/min/1.73 m\^2 based on MDRD formula at screening visit
  • Type I or II diabetes mellitus
  • Documented history of prior MI
  • Atrial fibrillation as noted by ECG, associated with index MI
  • LVEF \<30% associated with index MI
  • Worst Killip class III or IV associated with index MI requiring intravenous treatment
  • STEMI without reperfusion therapy within the first 24 hours after presentation
  • Hemodynamically stable defined as:
  • +3 more criteria

You may not qualify if:

  • Known history of chronic HF prior to randomization
  • Cardiogenic shock within the last 24 hours prior to randomization
  • Persistent clinical HF at the time of randomization
  • Coronary artery bypass graft (CABG) performed or planned for index MI
  • Clinically significant right ventricular MI as index MI
  • Symptomatic hypotension at screening or randomization
  • Patients with a known history of angioedema
  • Stroke or transient ischemic attack within one month prior to randomization
  • Known or suspected bilateral renal artery stenosis
  • Clinically significant obstructive cardiomyopathy
  • Open-heart surgery performed within one month prior to randomization or planned cardiac surgery w/in the 3 months prior to randomization
  • eGFR \< 30 ml/min/1.73 m\^2 as measured by MDRD at screening
  • Serum potassium \> 5.2 mmol /L (or equivalent plasma potassium value) at randomization
  • Known hepatic impairment (as evidenced by total bilirubin \> 3.0 mg/dL or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as esophageal varices
  • Previous use of LCZ696
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (486)

Novartis Investigative Site

Birmingham, Alabama, 35243, United States

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Novartis Investigative Site

Birmingham, Alabama, 35294-2041, United States

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Novartis Investigative Site

Huntsville, Alabama, 35801, United States

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Novartis Investigative Site

Gilbert, Arizona, 85297, United States

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Novartis Investigative Site

Bakersfield, California, 93301, United States

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Novartis Investigative Site

Carmichael, California, 95608, United States

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Novartis Investigative Site

Los Alamitos, California, 90720, United States

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Novartis Investigative Site

Northridge, California, 91325, United States

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Novartis Investigative Site

Orange, California, 92868, United States

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Novartis Investigative Site

San Francisco, California, 94143, United States

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Novartis Investigative Site

Sylmar, California, 91342, United States

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Novartis Investigative Site

Brandon, Florida, 33511, United States

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Novartis Investigative Site

Hollywood, Florida, 33312, United States

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Novartis Investigative Site

Jacksonville Beach, Florida, 32050, United States

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Novartis Investigative Site

Ocala, Florida, 34480, United States

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Novartis Investigative Site

Cumming, Georgia, 30041, United States

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Novartis Investigative Site

Johns Creek, Georgia, 30024, United States

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Novartis Investigative Site

Thomasville, Georgia, 31792, United States

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Novartis Investigative Site

Boise, Idaho, 83702, United States

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Novartis Investigative Site

Coeur d'Alene, Idaho, 83814, United States

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Novartis Investigative Site

Muncie, Indiana, 47303-3400, United States

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Novartis Investigative Site

Munster, Indiana, 46321, United States

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Novartis Investigative Site

Richmond, Indiana, 47374, United States

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Novartis Investigative Site

Iowa City, Iowa, 52242, United States

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Novartis Investigative Site

Alexandria, Louisiana, 71301, United States

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Novartis Investigative Site

Baton Rouge, Louisiana, 70808, United States

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Novartis Investigative Site

Covington, Louisiana, 70433, United States

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Novartis Investigative Site

Hammond, Louisiana, 70403, United States

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Novartis Investigative Site

Slidell, Louisiana, 70458, United States

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Novartis Investigative Site

Bangor, Maine, 04401, United States

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Novartis Investigative Site

Baltimore, Maryland, 21201, United States

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Novartis Investigative Site

Baltimore, Maryland, 21218, United States

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Novartis Investigative Site

Rockville, Maryland, 20850, United States

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Novartis Investigative Site

Detroit, Michigan, 48201, United States

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Novartis Investigative Site

Kalamazoo, Michigan, 49008, United States

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Novartis Investigative Site

Lansing, Michigan, 48912, United States

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Novartis Investigative Site

Petoskey, Michigan, 49770, United States

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Novartis Investigative Site

Saginaw, Michigan, 48601, United States

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Novartis Investigative Site

Southfield, Michigan, 48075, United States

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Novartis Investigative Site

Duluth, Minnesota, 55805, United States

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Novartis Investigative Site

Robbinsdale, Minnesota, 55422, United States

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Novartis Investigative Site

Saint Cloud, Minnesota, 56303, United States

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Novartis Investigative Site

Saint Paul, Minnesota, 55101, United States

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Novartis Investigative Site

Hattiesburg, Mississippi, 39401, United States

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Novartis Investigative Site

Jackson, Mississippi, 39216, United States

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Novartis Investigative Site

Lee's Summit, Missouri, 64064, United States

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Novartis Investigative Site

North Kansas City, Missouri, 64116, United States

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Novartis Investigative Site

Springfield, Missouri, 65804, United States

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Novartis Investigative Site

Lincoln, Nebraska, 68506, United States

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Novartis Investigative Site

Lincoln, Nebraska, 68526, United States

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Novartis Investigative Site

Omaha, Nebraska, 68114, United States

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Novartis Investigative Site

Lebanon, New Hampshire, 03756, United States

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Novartis Investigative Site

Hackensack, New Jersey, 07601, United States

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Novartis Investigative Site

Flushing, New York, 11355, United States

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Novartis Investigative Site

New York, New York, 10016, United States

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Novartis Investigative Site

New York, New York, 10029, United States

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Novartis Investigative Site

Valhalla, New York, 10595, United States

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Novartis Investigative Site

Chapel Hill, North Carolina, 27599, United States

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Novartis Investigative Site

Charlotte, North Carolina, 28204, United States

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Novartis Investigative Site

Durham, North Carolina, 27710, United States

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Novartis Investigative Site

Grand Forks, North Dakota, 58201, United States

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Canton, Ohio, 44710, United States

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Cincinnati, Ohio, 45220, United States

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Medford, Oregon, 97504, United States

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Erie, Pennsylvania, 16550, United States

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Hershey, Pennsylvania, 17033, United States

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Novartis Investigative Site

York, Pennsylvania, 17403, United States

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Novartis Investigative Site

Charleston, South Carolina, 29403, United States

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Columbia, South Carolina, 29203, United States

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Greenville, South Carolina, 29607, United States

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Novartis Investigative Site

Rapid City, South Dakota, 57701, United States

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Knoxville, Tennessee, 37917, United States

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Nashville, Tennessee, 37212, United States

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Novartis Investigative Site

Dallas, Texas, 75226, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

Webster, Texas, 77598, United States

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Novartis Investigative Site

Danville, Virginia, 24541, United States

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Novartis Investigative Site

Falls Church, Virginia, 22042, United States

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Lynchburg, Virginia, 24501, United States

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Novartis Investigative Site

Manassas, Virginia, 20109, United States

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Novartis Investigative Site

Bellevue, Washington, 98004, United States

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Novartis Investigative Site

Caba, Buenos Aires, C1280AEB, Argentina

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La Plata, Buenos Aires, B1900AWT, Argentina

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Novartis Investigative Site

Buenos Aires, Buenos Aires F.D., C1078AAI, Argentina

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Novartis Investigative Site

Salta, Salta Province, A4406BPF, Argentina

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Novartis Investigative Site

San Miguel de Tucumán, San Miguel de Tucuman, T4000ICL, Argentina

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Rosario, Santa Fe Province, C2000DSR, Argentina

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Rosario, Santa Fe Province, S2000DSV, Argentina

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Novartis Investigative Site

San Miguel de Tucumán, Tucumán Province, T4000IFL, Argentina

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Buenos Aires, B1602ABQ, Argentina

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Buenos Aires, B1846BMF, Argentina

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Buenos Aires, C1405CNF, Argentina

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Buenos Aires, C1428DCO, Argentina

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Buenos Aires, C1430EGF, Argentina

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Corrientes, W3400, Argentina

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Córdoba, X5000, Argentina

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Córdoba, X5003DCP, Argentina

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Córdoba, X5004BAL, Argentina

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Córdoba, X5006CBI, Argentina

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Formosa, P3600, Argentina

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San Luis, D5702JRS, Argentina

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Santa Fe, S3000FUJ, Argentina

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Chemside, Queensland, 4032, Australia

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Herston, Queensland, 4029, Australia

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Bedford Park, South Australia, 5041, Australia

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Novartis Investigative Site

Hobart, Tasmania, 7000, Australia

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Novartis Investigative Site

Geelong, Victoria, 3220, Australia

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Murdoch, Western Australia, 6150, Australia

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Innsbruck, Tyrol, 6020, Austria

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Braunau am Inn, A5280, Austria

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Graz, 8036, Austria

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Linz, A-4010, Austria

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Salzburg, 5020, Austria

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Novartis Investigative Site

Sankt Pölten, 3100, Austria

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Novartis Investigative Site

Vienna, 1210, Austria

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Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

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Novartis Investigative Site

Aalst, 9300, Belgium

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Novartis Investigative Site

Brasschaat, 2930, Belgium

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Genk, 3600, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Turnhout, 2300, Belgium

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Novartis Investigative Site

Yvoir, 5530, Belgium

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Novartis Investigative Site

Fortaleza, Ceará, 60430 370, Brazil

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Novartis Investigative Site

Goiânia, Goiás, 74605 050, Brazil

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Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30140 062, Brazil

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Novartis Investigative Site

Uberlândia, Minas Gerais, 38411 186, Brazil

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Novartis Investigative Site

Curitiba, Paraná, 80730 150, Brazil

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Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90620 001, Brazil

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Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 91350 200, Brazil

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Novartis Investigative Site

Blumenau, Santa Catarina, 89010 500, Brazil

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Novartis Investigative Site

Campinas, São Paulo, 13060 080, Brazil

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Novartis Investigative Site

São José do Rio Preto, São Paulo, 15090 000, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

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Novartis Investigative Site

Campina Grande do Sul, 83430 000, Brazil

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Novartis Investigative Site

São José, 8001, Brazil

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Novartis Investigative Site

Burgas, BGR, 8018, Bulgaria

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Novartis Investigative Site

Sofia, BGR, 1407, Bulgaria

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Novartis Investigative Site

Blagoevgrad, 2700, Bulgaria

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Novartis Investigative Site

Burgas, 8127, Bulgaria

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Novartis Investigative Site

Gabrovo, 5300, Bulgaria

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Novartis Investigative Site

Kardzhali, 6600, Bulgaria

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Novartis Investigative Site

Pernik, 2300, Bulgaria

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Novartis Investigative Site

Pleven, 5800, Bulgaria

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Novartis Investigative Site

Plovdiv, 4002, Bulgaria

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Novartis Investigative Site

Rousse, 7000, Bulgaria

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Novartis Investigative Site

Sofia, 1202, Bulgaria

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Novartis Investigative Site

Sofia, 1233, Bulgaria

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Novartis Investigative Site

Sofia, 1431, Bulgaria

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Novartis Investigative Site

Sofia, 1527, Bulgaria

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Novartis Investigative Site

Sofia, 1606, Bulgaria

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Novartis Investigative Site

Sofia, 1709, Bulgaria

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Novartis Investigative Site

Varna, 9010, Bulgaria

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Novartis Investigative Site

Edmonton, Alberta, T6G 2E1, Canada

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Victoria, British Columbia, V8R4R2, Canada

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Novartis Investigative Site

Ottawa, Ontario, K1Y 4W7, Canada

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Novartis Investigative Site

Toronto, Ontario, M5B 1W8, Canada

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Novartis Investigative Site

Montreal, Quebec, H1T 1C8, Canada

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Novartis Investigative Site

Sainte-Foy, Quebec, G1V 4G5, Canada

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Novartis Investigative Site

Terrebonne, Quebec, J6V 2H2, Canada

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Novartis Investigative Site

Trois-Rivières, Quebec, G8Z 3R9, Canada

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Novartis Investigative Site

Beijing, Beijing Municipality, 100037, China

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Novartis Investigative Site

Xicheng, Beijing Municipality, 100044, China

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Novartis Investigative Site

Lanzhou, Gansu, 730030, China

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Guangzhou, Guangdong, 51000, China

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Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

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Novartis Investigative Site

Shijiazhuang, Hebei, 050000, China

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Novartis Investigative Site

Harbin, Heilongjiang, 150000, China

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Novartis Investigative Site

Wuhan, Hubei, 430060, China

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Changsha, Hunan, 410011, China

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Nanjing, Jiangsu, 210008, China

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Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

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Novartis Investigative Site

Changchun, Jilin, 130021, China

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Novartis Investigative Site

Yanji, Jilin, 133001, China

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Novartis Investigative Site

Shengyang, Liaoning, 110016, China

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Novartis Investigative Site

Jinan, Shandong, 250013, China

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Novartis Investigative Site

Shanghai, Shanghai Municipality, 200120, China

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Novartis Investigative Site

Zhujing, Shanghai Municipality, 201508, China

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Novartis Investigative Site

Xian, Shanxi, 710061, China

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Novartis Investigative Site

Tianjin, Tianjin Municipality, 300121, China

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Novartis Investigative Site

Wenzhou, Zhejiang, 325000, China

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Novartis Investigative Site

Beijing, 100029, China

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Novartis Investigative Site

Beijing, 100050, China

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Novartis Investigative Site

Beijing, 100191, China

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Novartis Investigative Site

Shanghai, 200080, China

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Novartis Investigative Site

Tianjin, 300052, China

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Novartis Investigative Site

Wuhan, 430022, China

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Novartis Investigative Site

Medellín, Antioquia, 050001, Colombia

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Novartis Investigative Site

Medellín, Antioquia, 6CM8+47, Colombia

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Novartis Investigative Site

Bucaramanga, Santander Department, 65265, Colombia

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Novartis Investigative Site

Cali, Valle del Cauca Department, 760001, Colombia

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Novartis Investigative Site

Barranquilla, 080020, Colombia

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Novartis Investigative Site

Bogotá, 110010, Colombia

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Novartis Investigative Site

Zagreb, HRV, 10000, Croatia

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Novartis Investigative Site

Čakovec, 40000, Croatia

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Novartis Investigative Site

Zagreb, 10000, Croatia

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Novartis Investigative Site

Kladno, Czech Republic, 272 00, Czechia

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Novartis Investigative Site

Liberec, Czech Republic, 46063, Czechia

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Novartis Investigative Site

Zlín, Czech Republic, 762 75, Czechia

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Novartis Investigative Site

Brno-Bohunice, 625 00, Czechia

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Novartis Investigative Site

Plzen-Bory, 305 99, Czechia

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Novartis Investigative Site

Prague, 100 34, Czechia

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Novartis Investigative Site

Prague, 12808, Czechia

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Novartis Investigative Site

Prague, 146 24, Czechia

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Novartis Investigative Site

Aalborg, DK 9000, Denmark

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Novartis Investigative Site

Glostrup Municipality, 2600, Denmark

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Novartis Investigative Site

Herlev, 2730, Denmark

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Hvidovre, 2650, Denmark

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Svendborg, 5700, Denmark

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Novartis Investigative Site

Vejle, 7100, Denmark

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Novartis Investigative Site

Viborg, DK-8800, Denmark

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Novartis Investigative Site

Jyväskylä, 40620, Finland

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Kaupio, 70210, Finland

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Tampere, 33520, Finland

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Novartis Investigative Site

Bron, 69677, France

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Chambray-lès-Tours, 37170, France

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Novartis Investigative Site

Corbeil-Essonnes, 91100, France

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Novartis Investigative Site

Grenoble, 38043, France

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Marseille, 13008, France

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Paris, 75010, France

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Novartis Investigative Site

Paris, 75015, France

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Novartis Investigative Site

Paris, 75877, France

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Novartis Investigative Site

Pessac, 33604, France

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Novartis Investigative Site

Toulouse, 31059, France

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Novartis Investigative Site

Augsburg, 86179, Germany

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Novartis Investigative Site

Bad Krozingen, 79189, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Bremen, 28277, Germany

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Coburg, 96450, Germany

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Cologne, 50937, Germany

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Dresden, 01307, Germany

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Novartis Investigative Site

Erfurt, 99089, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Novartis Investigative Site

Esslingen am Neckar, 73730, Germany

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Novartis Investigative Site

Frankfurt, 60590, Germany

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Novartis Investigative Site

Frankfurt, 65929, Germany

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Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

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Novartis Investigative Site

Greifswald, 17475, Germany

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Novartis Investigative Site

Gütersloh, 33332, Germany

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Novartis Investigative Site

Hennigsdorf, 16761, Germany

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Novartis Investigative Site

Kiel, 24105, Germany

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Novartis Investigative Site

Koeln-Nippes, 50733, Germany

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Novartis Investigative Site

Langen, 63225, Germany

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Novartis Investigative Site

Leverkusen, 51375, Germany

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Novartis Investigative Site

Ludwigshafen, 67063, Germany

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Novartis Investigative Site

Mönchengladbach, 41063, Germany

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Novartis Investigative Site

Neuss, 41464, Germany

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Novartis Investigative Site

Neuwied, 56564, Germany

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Novartis Investigative Site

Riesa, 01589, Germany

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Novartis Investigative Site

Rüsselsheim am Main, 65428, Germany

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Novartis Investigative Site

Stadtlohn, 48703, Germany

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Novartis Investigative Site

Vechta, 49377, Germany

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Novartis Investigative Site

Villingen-Schwenningen, 78052, Germany

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Novartis Investigative Site

Witten, 58455, Germany

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Novartis Investigative Site

Würzburg, 97080, Germany

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Novartis Investigative Site

Alexandroupoli, Evros, 681 00, Greece

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Novartis Investigative Site

Athens, GR, 115 27, Greece

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Novartis Investigative Site

Athens, GR, 14233, Greece

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Novartis Investigative Site

Larissa, GR, 411 10, Greece

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Novartis Investigative Site

Athens, 115 21, Greece

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Novartis Investigative Site

Athens, 115 27, Greece

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Novartis Investigative Site

Athens, 115 28, Greece

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Novartis Investigative Site

Athens, 12462, Greece

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Novartis Investigative Site

Pécs, Baranya, 7621, Hungary

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Novartis Investigative Site

Zalaegerszeg, Zala County, 8900, Hungary

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Novartis Investigative Site

Budapest, 1027, Hungary

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Novartis Investigative Site

Budapest, 1085, Hungary

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Novartis Investigative Site

Budapest, 1134, Hungary

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Budapest, H 1096, Hungary

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Novartis Investigative Site

Debrecen, 4032, Hungary

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Novartis Investigative Site

Szeged, 6725, Hungary

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Novartis Investigative Site

Székesfehérvár, H-8000, Hungary

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Novartis Investigative Site

Ahmedabad, Gujarat, 380 060, India

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Novartis Investigative Site

Karamsad, Gujarat, 388325, India

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Vadodara, Gujarat, 390022, India

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Novartis Investigative Site

Gurgaon, Haryana, 122001, India

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Novartis Investigative Site

Kochi, Kerala, 682 018, India

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Novartis Investigative Site

Mumbai, Maharashtra, 400012, India

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Novartis Investigative Site

Nagpur, Maharashtra, 440009, India

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Novartis Investigative Site

Nashik, Maharashtra, 422005, India

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Novartis Investigative Site

Pune, Maharashtra, 411001, India

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Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110 060, India

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Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110007, India

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Novartis Investigative Site

Bikaner, Rajasthan, 334003, India

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Novartis Investigative Site

Madurai, Tamil Nadu, 625107, India

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Novartis Investigative Site

Hyderabad, Telangana, 500082, India

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Novartis Investigative Site

Secunderabad, Telangana, 500003, India

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Novartis Investigative Site

Dehradun, Uttarakhand, 248001, India

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Novartis Investigative Site

Lower Galilee, Israel, 15208, Israel

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Novartis Investigative Site

Ashkelon, 78278, Israel

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Novartis Investigative Site

Haifa, 3109601, Israel

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Novartis Investigative Site

Petah Tikva, 49100, Israel

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Novartis Investigative Site

Sefad, 13100, Israel

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Novartis Investigative Site

Tel Aviv, 6423906, Israel

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Bergamo, BG, 24127, Italy

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Bologna, BO, 40133, Italy

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Novartis Investigative Site

Brescia, BS, 25123, Italy

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Novartis Investigative Site

Catanzaro, CZ, 88100, Italy

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Novartis Investigative Site

Cona, FE, 44121, Italy

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Novartis Investigative Site

Grosseto, GR, 58100, Italy

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Sanremo, IM, 18038, Italy

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Novartis Investigative Site

Milan, MI, 20138, Italy

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Milan, MI, 20142, Italy

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Novartis Investigative Site

Milan, MI, 20162, Italy

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Novartis Investigative Site

Pavia, PV, 27100, Italy

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Novartis Investigative Site

Roma, RM, 00161, Italy

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Novartis Investigative Site

Roma, RM, 00184, Italy

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Novartis Investigative Site

Rimini, RN, 47900, Italy

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Novartis Investigative Site

Trieste, TS, 34149, Italy

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Napoli, 80131, Italy

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Novartis Investigative Site

Torreón, Coahulia, 27000, Mexico

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Guadalajara, Jalisco, 44670, Mexico

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Guadalajara, Jalisco, 45116, Mexico

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Culiacan Sinaloa, Mexico City, 80230, Mexico

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Mexico City, 02980, Mexico

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Novartis Investigative Site

Querétaro, 76000, Mexico

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San Luis Potosí City, 78240, Mexico

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Sneek, The Netherlands, 8601 ZR, Netherlands

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Alkmaar, 1815 JD, Netherlands

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Almelo, 7609 PP, Netherlands

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Amersfoort, 3813 TZ, Netherlands

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Amsterdam, 1091AC, Netherlands

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Beverwijk, NL-1942 LE, Netherlands

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Breda, 4818 CK, Netherlands

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Ede, 6716 RP, Netherlands

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Gouda, 2803 HH, Netherlands

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Groningen, 9713 GZ, Netherlands

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Heemstede, 2102 CW, Netherlands

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Leeuwarden, 8934 AD, Netherlands

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Leiderdorp, 2353 GA, Netherlands

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Rotterdam, 3015 CE, Netherlands

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Rotterdam, 3045 PM, Netherlands

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Rotterdam, 3083 AN, Netherlands

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Tilburg, 5042 AD, Netherlands

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Uden, 5406 PT, Netherlands

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Novartis Investigative Site

Veldhoven, 5504 DB, Netherlands

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Novartis Investigative Site

Venlo, 5912 BL, Netherlands

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Novartis Investigative Site

Zutphen, 7207 AE, Netherlands

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Novartis Investigative Site

Zwolle, 8025 AB, Netherlands

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Novartis Investigative Site

Grålum, 1714, Norway

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Novartis Investigative Site

Oslo, 0372, Norway

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Stavanger, 4068, Norway

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Bellavista, Lima region, CALLAO 02, Peru

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Jesus Maria, Lima region, 11, Peru

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Novartis Investigative Site

Lima Cercado, Lima region, 01, Peru

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Novartis Investigative Site

Lima, 10, Peru

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Novartis Investigative Site

Iloilo City, Iloilo, 5000, Philippines

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Quezon City, Manila, 1100, Philippines

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Novartis Investigative Site

Manila, National Capital Region, 1000, Philippines

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Bialystok, 15 276, Poland

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Lubin, 59-301, Poland

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Lublin, 20-718, Poland

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Warsaw, 02-097, Poland

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Warsaw, 02-507, Poland

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Novartis Investigative Site

Carnaxide, Lisbon District, 2799 523, Portugal

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Almada, 2801 951, Portugal

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Novartis Investigative Site

Braga, 4710243, Portugal

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Novartis Investigative Site

Coimbra, 3041-853, Portugal

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Novartis Investigative Site

Covilha, 6200-251, Portugal

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Novartis Investigative Site

Faro, 8000 386, Portugal

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Novartis Investigative Site

Guimarães, 4835 044, Portugal

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Novartis Investigative Site

Leiria, 2410-187, Portugal

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Novartis Investigative Site

Lisbon, 1649-035, Portugal

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Novartis Investigative Site

Vila Real, 5000-508, Portugal

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Novartis Investigative Site

Piteşti, Argeş, 110438, Romania

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Novartis Investigative Site

Bucharest, District 4, 4204179, Romania

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Oradea, Jud Bihor, 410169, Romania

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Cluj-Napoca, Jud Cluj, 400001, Romania

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Novartis Investigative Site

Iași, Jud Iasi, 700732, Romania

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Novartis Investigative Site

Târgu Mureş, Mureș County, 540124, Romania

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Novartis Investigative Site

Brăila, ROM, 810249, Romania

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Novartis Investigative Site

Suceava, ROM, 727525, Romania

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Novartis Investigative Site

Timișoara, Timiș County, 300362, Romania

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Baia Mare, 430031, Romania

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Novartis Investigative Site

Bucharest, 011461, Romania

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Bucharest, 014461, Romania

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Bucharest, 022322, Romania

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Novartis Investigative Site

Bucharest, 041915, Romania

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Bucharest, 050098, Romania

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Craiova, 200642, Romania

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Sibiu, 550245, Romania

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Novartis Investigative Site

Timișoara, 300041, Romania

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Novartis Investigative Site

Timișoara, 300310, Romania

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Novartis Investigative Site

Barnaul, 656038, Russia

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Kemerovo, 650002, Russia

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Krasnodar, 350086, Russia

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Moscow, 115516, Russia

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Moscow, 117292, Russia

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Moscow, 121359, Russia

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Moscow, 121552, Russia

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Moscow, 127644, Russia

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Murmansk, 183047, Russia

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Novartis Investigative Site

N.Novgorod, 603005, Russia

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Nizhny Novgorod, 603126, Russia

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Novartis Investigative Site

Rostov-on-Don, 344068, Russia

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S.-Petersburg, 192242, Russia

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Saint Petersburg, 191014, Russia

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Novartis Investigative Site

Saint Petersburg, 191015, Russia

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Saint Petersburg, 194044, Russia

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Novartis Investigative Site

Saint Petersburg, 194291, Russia

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Saint Petersburg, 197341, Russia

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Saratov, 410012, Russia

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Sestroretsk, 197706, Russia

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Sochy, 354057, Russia

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Tomsk, 634012, Russia

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Novartis Investigative Site

Yekaterinburg, 620109, Russia

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Novartis Investigative Site

Singapore, 119074, Singapore

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Novartis Investigative Site

Singapore, 169609, Singapore

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Singapore, 308433, Singapore

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Novartis Investigative Site

Singapore, 529889, Singapore

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Novartis Investigative Site

Singapore, 768828, Singapore

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Novartis Investigative Site

Bratislava, Slovak Republic, 826 06, Slovakia

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Nitra, Slovak Republic, 949 01, Slovakia

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Banská Bystrica, SVK, 974 01, Slovakia

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Novartis Investigative Site

Bratislava, 833 48, Slovakia

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Košice, 040 11, Slovakia

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Prešov, 081 81, Slovakia

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Pinelands, Cape Town, 7405, South Africa

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Cape Town, Western Cape, 7500, South Africa

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George, Western Cape, 6529, South Africa

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Cape Town, 7925, South Africa

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Worcester, 6850, South Africa

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Wŏnju, Gangwon-do, 26427, South Korea

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Cheongju-si, North Chungcheong, 28644, South Korea

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Novartis Investigative Site

Gwangju, 61469, South Korea

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Novartis Investigative Site

Seoul, 02841, South Korea

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Málaga, Andalusia, 29010, Spain

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Seville, Andalusia, 41014, Spain

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Villamartín, Cadiz, 11650, Spain

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Novartis Investigative Site

León, Castille and León, 24071, Spain

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Novartis Investigative Site

Badalona, Catalonia, 08916, Spain

Location

Novartis Investigative Site

Cáceres, Extremadura, 10003, Spain

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A Coruña, Galicia, 15006, Spain

Location

Novartis Investigative Site

El Palmar, Murcia, 30120, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Valencia, 46026, Spain

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Novartis Investigative Site

Stockholm, SE, 141 86, Sweden

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Novartis Investigative Site

Goethenburg, 413 45, Sweden

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Novartis Investigative Site

Helsingborg, 252 20, Sweden

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Novartis Investigative Site

Helsingborg, 25232, Sweden

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Novartis Investigative Site

Malmo, 221 85, Sweden

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Stockholm, 118 83, Sweden

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Uppsala, 751 85, Sweden

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Novartis Investigative Site

Västerås, 72189, Sweden

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Bern, 3010, Switzerland

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Lucerne, CH 6000, Switzerland

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Lugano, 6903, Switzerland

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Sankt Gallen, 9007, Switzerland

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Novartis Investigative Site

New Taipei City, 22060, Taiwan

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Taichung, 40447, Taiwan

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Tainan, 71004, Taiwan

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Novartis Investigative Site

Taipei, 10002, Taiwan

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Novartis Investigative Site

Taipei, 10449, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

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Novartis Investigative Site

Taoyuan District, 33305, Taiwan

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Novartis Investigative Site

Yilan, 26058, Taiwan

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Novartis Investigative Site

Bangkok, THA, 10330, Thailand

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Novartis Investigative Site

Khon Kaen, THA, 40002, Thailand

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Novartis Investigative Site

Bangkok, 10700, Thailand

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Novartis Investigative Site

Chiang Mai, 50200, Thailand

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Novartis Investigative Site

Meselik, Eskişehir, 26480, Turkey (Türkiye)

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Novartis Investigative Site

Ankara-Cankaya, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34304, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34865, Turkey (Türkiye)

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Izmir, 35040, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

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Kucukcekmece Istanbul, 34303, Turkey (Türkiye)

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Novartis Investigative Site

Mersin, 33343, Turkey (Türkiye)

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Sivas, 58140, Turkey (Türkiye)

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Trabzon, 61080, Turkey (Türkiye)

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Basingstoke, Hampshire, RG24 9NA, United Kingdom

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Lincoln, Lincolnshire, LN2 5QY, United Kingdom

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Novartis Investigative Site

Craigavon, Northern Ireland, BT63 5QQ, United Kingdom

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Novartis Investigative Site

Clydebank, West Dumbartonshire, G81 4HX, United Kingdom

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Novartis Investigative Site

Belfast, BT12 6BA, United Kingdom

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Birmingham, B9 5SS, United Kingdom

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Bournemouth, BH7 7DW, United Kingdom

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Glasgow, G51 4TF, United Kingdom

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Leeds, LS1 3EX, United Kingdom

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Leicester, LE3 9QP, United Kingdom

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Middlesbrough, TS4 3BW, United Kingdom

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Newcastle upon Tyne, NE7 7DN, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Novartis Investigative Site

Worcester, WR5 1DD, United Kingdom

Location

Related Publications (9)

  • Curtain JP, Pfeffer MA, Braunwald E, Claggett BL, Granger CB, Kober L, Lewis EF, Maggioni AP, Mann DL, Rouleau JL, Solomon SD, Steg PG, Finn PV, Fernandez A, Jering KS, McMurray JJV. Rates of Sudden Death After Myocardial Infarction-Insights From the VALIANT and PARADISE-MI Trials. JAMA Cardiol. 2024 Oct 1;9(10):928-933. doi: 10.1001/jamacardio.2024.2356.

  • Mann DL, Nicolas J, Claggett B, Miao ZM, Granger CB, Kerkar P, Kober L, Lewis EF, McMurray JJV, Maggioni AP, Nunez J, Ntsekhe M, Rouleau JL, Sim D, Solomon SD, Steg PG, van der Meer P, Braunwald E, Pfeffer MA, Mehran R. Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI. J Am Coll Cardiol. 2024 Mar 5;83(9):904-914. doi: 10.1016/j.jacc.2024.01.002.

  • Petrie MC, Rouleau JL, Claggett B, Jering K, van der Meer P, Kober L, Miao ZM, Lewis E, Granger C, De Pasqulae CG, Mann D, Steg PG, Maggioni A, Amir O, Lefkowitz M, Braunwald E, Solomon SD, McMurray JJV, Pfeffer MA. Pulmonary Congestion and Left Ventricular Dysfunction After Myocardial Infarction: Insights From the PARADISE-MI Trial. Circulation. 2024 Jan 23;149(4):335-338. doi: 10.1161/CIRCULATIONAHA.123.066163. Epub 2024 Jan 22. No abstract available.

  • Wang X, Jering KS, Cikes M, Tokmakova MP, Mehran R, Han Y, East C, Mody FV, Wang Y, Lewis EF, Claggett B, McMurray JJV, Granger CB, Pfeffer MA, Solomon SD. Sex Differences in Clinical Characteristics and Outcomes After Myocardial Infarction With Low Ejection Fraction: Insights From PARADISE-MI. J Am Heart Assoc. 2023 Sep 5;12(17):e028942. doi: 10.1161/JAHA.122.028942. Epub 2023 Aug 23.

  • Jering KS, Claggett BL, Pfeffer MA, Granger CB, Kober L, Lewis EF, Maggioni AP, Mann DL, McMurray JJV, Prescott MF, Rouleau JL, Solomon SD, Steg PG, von Lewinski D, Braunwald E. Prognostic Importance of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Following High-Risk Myocardial Infarction in the PARADISE-MI Trial. Circ Heart Fail. 2023 May;16(5):e010259. doi: 10.1161/CIRCHEARTFAILURE.122.010259. Epub 2023 May 1.

  • Mehran R, Steg PG, Pfeffer MA, Jering K, Claggett B, Lewis EF, Granger C, Kober L, Maggioni A, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Ducrocq G, Berwanger O, De Pasquale CG, Landmesser U, Petrie M, Leng DSK, van der Meer P, Lefkowitz M, Zhou Y, Braunwald E. The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial. Circulation. 2022 Dec 6;146(23):1749-1757. doi: 10.1161/CIRCULATIONAHA.122.060841. Epub 2022 Nov 2.

  • Shah AM, Claggett B, Prasad N, Li G, Volquez M, Jering K, Cikes M, Kovacs A, Mullens W, Nicolau JC, Kober L, van der Meer P, Jhund PS, Ibram G, Lefkowitz M, Zhou Y, Solomon SD, Pfeffer MA. Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy. Circulation. 2022 Oct 4;146(14):1067-1081. doi: 10.1161/CIRCULATIONAHA.122.059210. Epub 2022 Sep 9.

  • Pfeffer MA, Claggett B, Lewis EF, Granger CB, Kober L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, Fernandez A, Filippatos G, Jering K, Landmesser U, Menon V, Merkely B, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Wang Y, Braunwald E. Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial. Circulation. 2022 Jan 4;145(1):87-89. doi: 10.1161/CIRCULATIONAHA.121.057429. Epub 2021 Nov 19. No abstract available.

  • Pfeffer MA, Claggett B, Lewis EF, Granger CB, Kober L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, East C, Fernandez A, Jering K, Landmesser U, Mehran R, Merkely B, Vaghaiwalla Mody F, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Gong J, Braunwald E; PARADISE-MI Investigators and Committees. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction. N Engl J Med. 2021 Nov 11;385(20):1845-1855. doi: 10.1056/NEJMoa2104508.

MeSH Terms

Conditions

Ventricular Dysfunction, LeftST Elevation Myocardial InfarctionNon-ST Elevated Myocardial Infarction

Interventions

sacubitril and valsartan sodium hydrate drug combinationsacubitrilValsartanRamipril

Condition Hierarchy (Ancestors)

Ventricular DysfunctionHeart DiseasesCardiovascular DiseasesMyocardial InfarctionMyocardial IschemiaVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Intervention Hierarchy (Ancestors)

TetrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsValineAmino Acids, Branched-ChainAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, EssentialHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Limitations and Caveats

In this study there were 25 patients who did not take study treatment after randomization, and thus were not included in the safety set.

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 4, 2016

First Posted

October 5, 2016

Study Start

December 9, 2016

Primary Completion

February 26, 2021

Study Completion

February 26, 2021

Last Updated

June 22, 2023

Results First Posted

June 22, 2023

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will share

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Locations