Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients

NCT01922089 | Completed Phase 2 Results

• 2 other identifiers: CLCZ696B22282013-001835-33
• Study Type: interventional
• Target: 498
• Locations: 11 countries
• Sites: 105

Brief Summary

The purpose of this study is to assess the safety and tolerability of initiating LCZ696 in heart failure patients with reduced ejection fraction (HF-rEF) using conservative (reaching target dose over 6 weeks) and condensed (reaching target dose over 3 weeks) up-titration regimens.

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

Heart failure, reduced ejection fraction, LCZ696, titration, safety, tolerability

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)

  Participants experiencing hypotension, renal dysfunction, hyperkalemia and angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving \> 160 mg of valsartan or \> 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving ≤ 160 mg of valsartan or ≤ 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)

  12 weeks

Secondary Outcomes (2)

• Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)

  12 weeks

• Number of Participants Who Tolerated Study Medication for at Least the Last Two Weeks of the Study and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low).

  12 weeks

Study Arms (2)

LCZ696 Condensed

EXPERIMENTAL

Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks

Drug: LCZ696

LCZ696 Conservative

EXPERIMENTAL

Up-titration to LCZ696 200 mg bid over 6 weeks

Drug: LCZ696

Interventions

LCZ696 DRUG

LCZ696 50 mg/100 mg/200 mg bid

LCZ696 Condensed; LCZ696 Conservative

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years; CHF with New York Heart Association class II-IV; left ventricular ejection fraction ≤ 35%; on beta blockers

You may not qualify if:

• Potassium \> 5.2 mmol/l; estimated glomerular filtration rate \< 30 ml/min/1.73 m2; systolic blood pressure \<100 mmHg or \> 180 mmHg; history of intolerance to recommended target doses of angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (105)

Novartis Investigative Site

Anchorage, Alaska, 99508, United States

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Novartis Investigative Site

Gilbert, Arizona, 85297, United States

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Novartis Investigative Site

Tucson, Arizona, 85710, United States

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Anaheim, California, 92801, United States

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Torrance, California, 90502, United States

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Atlantis, Florida, 33462, United States

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Chiefland, Florida, 32626, United States

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Aurora, Illinois, 60504, United States

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Peoria, Illinois, 61602, United States

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Evansville, Indiana, 47714, United States

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Slidell, Louisiana, 70458, United States

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Minneapolis, Minnesota, 55417, United States

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St Louis, Missouri, 63110, United States

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Buffalo, New York, 14215, United States

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Laurelton, New York, 11422, United States

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Marion, Ohio, 43302, United States

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Oak Ridge, Tennessee, 37830, United States

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Dallas, Texas, 75231, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

Houston, Texas, 77094, United States

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Livingston, Texas, 77351, United States

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Tacoma, Washington, 98405, United States

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Gabrovo, Bulgaria, 5300, Bulgaria

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Plovdiv, Bulgaria, 4000, Bulgaria

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Novartis Investigative Site

Plovdiv, Bulgaria, 4004, Bulgaria

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Novartis Investigative Site

Smolyan, Bulgaria, 4700, Bulgaria

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Sofia, 1202, Bulgaria

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Novartis Investigative Site

Sofia, 1407, Bulgaria

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Novartis Investigative Site

Jyväskylä, 40620, Finland

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Tampere, 33520, Finland

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Novartis Investigative Site

Bad Krozingen, 79189, Germany

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Berlin, 10367, Germany

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Novartis Investigative Site

Berlin, 10787, Germany

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Novartis Investigative Site

Berlin, 10789, Germany

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Novartis Investigative Site

Berlin, 13055, Germany

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Novartis Investigative Site

Berlin, 13347, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Berlin, 13405, Germany

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Novartis Investigative Site

Buch, 13125, Germany

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Novartis Investigative Site

Dietzenbach, 63128, Germany

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Ebersbach, 02730, Germany

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Frankfurt, 60594, Germany

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Göttingen, D-37075, Germany

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Novartis Investigative Site

Haßloch, 67454, Germany

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Huy / OT Anderbeck, 38836, Germany

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Ingelheim, 55218, Germany

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Kelkheim, 65779, Germany

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Novartis Investigative Site

Kleve, 47533, Germany

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Leipzig, 04315, Germany

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Mainz, 55116, Germany

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Mainz, 55131, Germany

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Mühlheim, 45468, Germany

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Siegen, 57072, Germany

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Straubing, 94315, Germany

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Würzburg, 97078, Germany

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Novartis Investigative Site

Budapest, 1042, Hungary

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Budapest, 1145, Hungary

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Budapest, H-1096, Hungary

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Debrecen, 4032, Hungary

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Mosonmagyaróvár, 9200, Hungary

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Novartis Investigative Site

Nyiregyháza, 4400, Hungary

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Pécs, 7623, Hungary

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Székesfehérvár, 8000, Hungary

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Aosta, AO, 11100, Italy

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Cortona, AR, 52044, Italy

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Bergamo, BG, 24128, Italy

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Bologna, BO, 40138, Italy

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Cona, FE, 44100, Italy

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Albano Laziale, RM, 00041, Italy

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Novartis Investigative Site

Roma, RM, 00163, Italy

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Sassari, SS, 07100, Italy

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Novartis Investigative Site

Vittorio Veneto, TV, 31029, Italy

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San Daniele del Friuli, UD, 33038, Italy

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Novartis Investigative Site

San Juan, 00936-6528, Puerto Rico

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Brezno, Slovak Republic, 977 42, Slovakia

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Novartis Investigative Site

Nitra, Slovak Republic, 949 01, Slovakia

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Svidník, Slovak Republic, 08901, Slovakia

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Novartis Investigative Site

Bratislava, Slovakia, 821 07, Slovakia

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Novartis Investigative Site

Bratislava, Slovakia, 83301, Slovakia

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Novartis Investigative Site

Košice, Slovakia, 040 01, Slovakia

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Novartis Investigative Site

Lučenec, Slovakia, 98439, Slovakia

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Novartis Investigative Site

Nové Zámky, Slovakia, 940 01, Slovakia

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Novartis Investigative Site

Trebišov, Slovakia, 075 01, Slovakia

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Novartis Investigative Site

Almería, Andalusia, 04120, Spain

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Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

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Novartis Investigative Site

Sanlúcar de Barrameda, Andalusia, 11540, Spain

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Novartis Investigative Site

Seville, Andalusia, 41014, Spain

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Novartis Investigative Site

Villamartín, Cadiz, 11650, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

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Novartis Investigative Site

Madrid, Madrid, 28007, Spain

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Novartis Investigative Site

Istanbul, Turkey, 34304, Turkey (Türkiye)

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Novartis Investigative Site

Haydarpasa/Istanbul, 34668, Turkey (Türkiye)

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Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

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Novartis Investigative Site

Mersin, 33079, Turkey (Türkiye)

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Novartis Investigative Site

Sivas, 58140, Turkey (Türkiye)

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Novartis Investigative Site

Dorchester, Dorset, DT1 2JY, United Kingdom

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Novartis Investigative Site

Saint Leonards-on-Sea, East Sussex, TN37 7RD, United Kingdom

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Novartis Investigative Site

Oldham, Lancashire, OL1 2JH, United Kingdom

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Novartis Investigative Site

Gateshead, Tyne and Wear, NE9 6SX, United Kingdom

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Bath, BA1 3NG, United Kingdom

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Bradford, BD9 6RJ, United Kingdom

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Coventry, CV2 2DX, United Kingdom

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Harrow, HA1 3UJ, United Kingdom

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Novartis Investigative Site

Nuneaton, CV10 7DJ, United Kingdom

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Related Publications (2)

• Senni M, McMurray JJV, Wachter R, McIntyre HF, Anand IS, Duino V, Sarkar A, Shi V, Charney A. Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study. Eur J Heart Fail. 2018 Mar;20(3):491-500. doi: 10.1002/ejhf.1054. Epub 2017 Nov 22.

  PMID: 29164797 DERIVED

• Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, Andreka P, Shehova-Yankova N, Anand I, Yilmaz MB, Gogia H, Martinez-Selles M, Fischer S, Zilahi Z, Cosmi F, Gelev V, Galve E, Gomez-Doblas JJ, Nociar J, Radomska M, Sokolova B, Volterrani M, Sarkar A, Reimund B, Chen F, Charney A. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016 Sep;18(9):1193-202. doi: 10.1002/ejhf.548. Epub 2016 May 12.

  PMID: 27170530 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: August 12, 2013
• First Posted: August 14, 2013
• Study Start: November 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 15, 2015
• Results First Posted: October 15, 2015

Record last verified: 2015-09

Locations

BU (6); SL (9); DE (25); IT (10); TU (5); GB (9); PR (1); ES (8); FI (2); HU (8); US (22)