Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF

NCT02007720 | Terminated Phase 3 Results DMC

• 1 other identifier: CRLX030A2302
• Study Type: interventional
• Target: 876
• Locations: 11 countries
• Sites: 132

Brief Summary

The purpose of the study was to evaluate the efficacy, safety and tolerability of intravenous infusion of serelaxin, when added to standard therapy, in acute heart failure (AHF) patients.

Conditions

Acute Heart Failure

Keywords

Serelaxin,; WHF,; Likert Scale,; RELAX-AHF-ASIA,; RLX030,; AHF,; acute heart failure

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change.

  The trichotomous clinical composite endpoint of treatment success, treatment failure, or no change. Treatment success defined as improvement of dyspnea by Likert scale and at least 2 points improvement by at least 2 physician assessed signs and symptoms (orthopnea, rales edema, and jugular venous pulse) at Day 2; treatment failure defined as worsening heart failure, death, or re-hospitalization due to heart failure or renal failure through Day 5; no change defined as neither the criteria for treatment success nor the criteria for treatment failure was met through Day 5.

  through day 5

Secondary Outcomes (13)

• Time to WHF

  Through Day 5

• Time to CV Death

  Through Day 180

• Time to All-cause Death

  Through Day 180

• Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days

  Through Day 5

• Dyspnea by VAS-AUC Changes

  Through Day 5

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients will receive continuous intravenous infusion of matching placebo serelaxin for 48 hours.

Drug: Placebo; Other: Standard of CareTherapy

Serelaxin

EXPERIMENTAL

Patients will receive continuous intravenous infusion of serelaxin(30 µg/kg/day) for 48 hours.

Drug: Serelaxin; Other: Standard of CareTherapy

Interventions

Serelaxin DRUG

Intravenous infusion

Serelaxin

Placebo DRUG

Intravenous infusion

Placebo

Standard of CareTherapy OTHER

This treatment can include but is not limited to intravenous and/or oral diuretics, ACE inhibitors/angiotensin receptor antagonists, β blockers, and aldosterone receptor antagonists, etc.

Placebo; Serelaxin

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 years of age, with body weight ≤160 kg
• Hospitalized for AHF; AHF is defined as including all of the following measured at any time between presentation (including the emergency department and outpatient clinic) and at the end of screening:
• Persistent dyspnea at rest or with minimal exertion at screening and at the time of randomization
• Pulmonary congestion on chest radiograph
• Brain natriuretic peptide (BNP) ≥500 pg/mL or NT-proBNP ≥2,000 pg/mL
• Systolic BP ≥125 mmHg at the start and at the end of screening
• Able to be randomized within 16 hours from presentation to the hospital, including the emergency department and outpatient clinic
• Received intravenous furosemide of at least 40 mg total (or equivalent) at any time between presentation (this includes outpatient clinic, ambulance, or hospital including emergency department) and the start of screening for the study for the treatment of the current acute HF episode
• Renal impairment defined as an estimate glomerular filtration rate using the between presentation and randomization of ≥ 25 and ≤75mL/min/1.73m2, calculated using the Modification of Diet in Renal Disease formula (or modified sMDRD formula according to specific ethnic groups and local practice guidelines).

You may not qualify if:

• Dyspnea primarily due to non-cardiac causes
• Temperature \>38.5°C (oral or equivalent), sepsis, active and clinically significant infection requiring IV anti-microbial treatment or known presence or evidence of Human Immunodeficiency Virus (HIV) infection (based on history and/or clinical findings, including laboratory results obtained during screening period).
• Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment
• \*Patients with systolic blood pressure \>180 mmHg at the end of screening
• AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate \<45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of \>130 beats per minute
• Hepatic disease unrelated to Heart Failure etiology and as determined by any one of the following: AST and/or ALT values exceeding 3 X ULN and/or bilirubin \> 1.5 X ULN at screening or history of hepatic encephalopathy, esophageal varices, or portacaval shunt, or a diagnosis of cirrhosis by any means, or evidence of chronic Hepatitis B (presence of hepatitis B surface antigen production: positive HBsAg), or chronic Hepatitis C infection (presence of Hepatitis C genetic replication: positive Hepatitis C viral RNA, based on history and/or clinical findings, including laboratory results obtained during screening period).
• \*Significant uncorrected left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area \<1.0 cm2 or mean gradient \>50 mmHg on prior or current echocardiogram), and severe mitral stenosis
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past year with a life expectancy less than 1 year

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (132)

Novartis Investigative Site

Beijing, Beijing Municipality, 100037, China

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Beijing, Beijing Municipality, 100039, China

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Lanzhou, Gansu, 730030, China

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Guangzhou, Guangdong, 51000, China

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Guangzhou, Guangdong, 510515, China

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Suzhou, Jiangsu, 215006, China

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Yangzhou, Jiangsu, China

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Shenyang, Liaoning, 110000, China

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Shenyang, Liaoning, 110003, China

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Shanghai, Shanghai Municipality, 200032, China

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Zhujing, Shanghai Municipality, 201508, China

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Xian, Shanxi, 710061, China

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Tianjin, Tianjin Municipality, 300121, China

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Hangzhou, Zhejiang, 310013, China

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Wenzhou, Zhejiang, 325000, China

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Beijing, 100050, China

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Chongqing, 400037, China

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Shanghai, China

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Ahmedabad, Gujarat, 380054, India

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Vadodara, Gujarat, 390022, India

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Rajasthan, India, 334003, India

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Nagpur, Maharashtra, 440010, India

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Nagpur, Maharashtra, 440012, India

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New Delhi, National Capital Territory of Delhi, 110029, India

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Chennai, Tamil Nadu, 600101, India

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Hyderabad, Telangana, 500082, India

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Nagakute, Aichi-ken, 480-1195, Japan

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Seto, Aichi-ken, 489-8642, Japan

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Kamogawa, Chiba, 2968602, Japan

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Saijō, Ehime, 793-0027, Japan

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Chikushino-shi, Fukuka, 818-8516, Japan

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Fukuoka, Fukuoka, 810-0001, Japan

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Fukuoka, Fukuoka, 811-0213, Japan

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Fukuoka, Fukuoka, 815-8588, Japan

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Iizuka, Fukuoka, 820-8505, Japan

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Kurume, Fukuoka, 830-8543, Japan

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Kurume, Fukuoka, 830-8577, Japan

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Ōgaki, Gifu, 503-8502, Japan

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Kushiro, Hokkaido, 085-0062, Japan

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Sapporo, Hokkaido, 006-8555, Japan

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Amagasaki, Hyōgo, 660 8550, Japan

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Kobe, Hyōgo, 654-0155, Japan

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Mito, Ibaraki, 311-4198, Japan

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Kanazawa, Ishikawa-ken, 920 8650, Japan

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Kan’onjichō, Kagawa-ken, 769-1695, Japan

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Takamatsu, Kagawa-ken, 760 8557, Japan

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Kawasaki, Kanagawa, 211-8533, Japan

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Yokohama, Kanagawa, 227-8501, Japan

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Yokohama, Kanagawa, 231-8682, Japan

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Yokohama, Kanagawa, 232 0024, Japan

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Yokohama, Kanagawa, 236 0051, Japan

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Kochi, Kochi, 781 8555, Japan

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Kumamoto, Kumamoto, 861-4193, Japan

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Yatsushiro, Kumamoto, 866-8660, Japan

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Kyoto, Kyoto, 607-8062, Japan

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Uji, Kyoto, 611-0042, Japan

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Sendai, Miyagi, 981-3133, Japan

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Nakano, Nagano, 383-8505, Japan

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Saku, Nagano, 3850051, Japan

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Ueda, Nagano, 386-8610, Japan

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Niigata, Niigata, 950-1197, Japan

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Osaka, Osaka, 540-0006, Japan

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Kawaguchi, Saitama, 333-0842, Japan

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Sayama, Saitama, 350-1323, Japan

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Wako, Saitama, 351-0102, Japan

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Kusatsu, Shiga, 525 8585, Japan

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Hamamatsu, Shizuoka, 430-8558, Japan

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Kakegawa, Shizuoka, 436-8555, Japan

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Akishima, Tokyo, 196-0003, Japan

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Chuo Ku, Tokyo, 104-8560, Japan

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Hachiōji, Tokyo, 192-0918, Japan

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Itabashi-ku, Tokyo, 173-8610, Japan

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Musashino, Tokyo, 180-8610, Japan

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Shinagawa Ku, Tokyo, 141 8625, Japan

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Shinagawa-ku, Tokyo, 142-8666, Japan

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Tanabe, Wakayama, 646-8558, Japan

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Osaka, 534-0021, Japan

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Saitama, 330 8503, Japan

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Amman, JOR, 11152, Jordan

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Amman, 11183, Jordan

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Amman, 11184, Jordan

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Beirut, 1107 2020, Lebanon

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Beirut, Lebanon

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El Achrafiyé, 166830, Lebanon

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Hazmiyeh, 470, Lebanon

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Kuala Lumpur, MYS, 56000, Malaysia

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Kota Kinabalu, Sabah, 88300, Malaysia

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Kuching, Sarawak, 94300, Malaysia

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Kuala Lumpur, Selangor, 43000, Malaysia

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Sungai Buloh, Selangor, 47000, Malaysia

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Kuala Lumpur, 50400, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Quezon City, Manila, 1100, Philippines

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Manila, National Capital Region, 1000, Philippines

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Makati City, 1229, Philippines

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Manila, 1003, Philippines

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Pasig, 1605, Philippines

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Quezon City, 1102, Philippines

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Quezon City, 1113, Philippines

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San Juan City, 1500, Philippines

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Singapore, 117549, Singapore

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Singapore, 169609, Singapore

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Gyeonggi-do, Bucheon Si, 422-711, South Korea

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Wŏnju, Gangwon-do, 26427, South Korea

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Bundang Gu, Gyeonggi-do, 13620, South Korea

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Seoul, Korea, 05505, South Korea

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Seoul, Korea, 06351, South Korea

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Seoul, Korea, 08308, South Korea

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Cheongju-si, North Chungcheong, 28644, South Korea

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Seoul, Seocho Gu, 06591, South Korea

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Busan, 602739, South Korea

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Gwangju, 61469, South Korea

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Incheon, 405 760, South Korea

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Seoul, 02841, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Changhua, 50006, Taiwan

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Kaohsiung City, 80756, Taiwan

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Kaohsiung City, 83301, Taiwan

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New Taipei City, 22060, Taiwan

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Taichung, 40447, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 10449, Taiwan

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Taipei, 11217, Taiwan

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Taoyuan District, 33305, Taiwan

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Yilan, 26058, Taiwan

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Songkhla, Hat Yai, 90110, Thailand

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Muang, 40002, Thailand

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Related Publications (2)

• Grand J, Miger K, Sajadieh A, Kober L, Torp-Pedersen C, Ertl G, Lopez-Sendon J, Pietro Maggioni A, Teerlink JR, Sato N, Gimpelewicz C, Metra M, Holbro T, Nielsen OW. Blood Pressure Drops During Hospitalization for Acute Heart Failure Treated With Serelaxin: A Patient-Level Analysis of 4 Randomized Controlled Trials. Circ Heart Fail. 2022 Apr;15(4):e009199. doi: 10.1161/CIRCHEARTFAILURE.121.009199. Epub 2022 Feb 21.

  PMID: 35184572 DERIVED

• Grand J, Miger K, Sajadieh A, Kober L, Torp-Pedersen C, Ertl G, Lopez-Sendon J, Pietro Maggioni A, Teerlink JR, Sato N, Gimpelewicz C, Metra M, Holbro T, Nielsen OW. Systolic Blood Pressure and Outcome in Patients Admitted With Acute Heart Failure: An Analysis of Individual Patient Data From 4 Randomized Clinical Trials. J Am Heart Assoc. 2021 Sep 21;10(18):e022288. doi: 10.1161/JAHA.121.022288. Epub 2021 Sep 13.

  PMID: 34514815 DERIVED

MeSH Terms

Interventions

serelaxin protein, human

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharma AG

novartis.email@novartis.com

+41613241111

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 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: November 20, 2013
• First Posted: December 11, 2013
• Study Start: March 12, 2014
• Primary Completion: March 27, 2017
• Study Completion: June 16, 2017
• Last Updated: August 2, 2019
• Results First Posted: August 2, 2019

Record last verified: 2019-06

Locations

IN (8); LE (4); PH (8); SG (2); TW (10); MY (7); TH (6); JO (3); CN (18); JP (52); KR (14)