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

Acute Heart Failure Clinical Trial

— RELAX-AHF-ASIA  

Official title:

A Multicenter, Randomized, Double-blind, Placebo Controlled Phase III Study to Evaluate the Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in Acute Heart Failure Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02007720
• Other study ID #: CRLX030A2302
• Status: Terminated
• Phase: Phase 3
• Start date: March 12, 2014
• Est. completion date: June 16, 2017

Study information

• Verified date: June 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 876
• Est. completion date: June 16, 2017
• Est. primary completion date: March 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Acute Heart Failure
• Heart Failure

Intervention

Drug:
• Serelaxin
Intravenous infusion
• Placebo
Intravenous infusion

Other:
• Standard of CareTherapy
This treatment can include but is not limited to intravenous and/or oral diuretics, ACE inhibitors/angiotensin receptor antagonists, ß blockers, and aldosterone receptor antagonists, etc.

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Jinshan	Shanghai
China	Novartis Investigative Site	Lanzhou	Gansu
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shanghai City
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Wenzhou	Zhejiang
China	Novartis Investigative Site	Xian	Shanxi
China	Novartis Investigative Site	Yangzhou	Jiangsu
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Rajasthan
India	Novartis Investigative Site	Vadodara	Gujarat
Japan	Novartis Investigative Site	Akishima-city	Tokyo
Japan	Novartis Investigative Site	Amagasaki city	Hyogo
Japan	Novartis Investigative Site	Chikushino-city	Fukuka
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Hachioji-city	Tokyo
Japan	Novartis Investigative Site	Hamamatsu-city	Shizuoka
Japan	Novartis Investigative Site	Iizuka-city	Fukuoka
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kakegawa-city	Shizuoka
Japan	Novartis Investigative Site	Kamogawa-city	Chiba
Japan	Novartis Investigative Site	Kanazawa	Ishikawa
Japan	Novartis Investigative Site	Kanonji-city	Kagawa
Japan	Novartis Investigative Site	Kawaguchi-city	Saitama
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Kobe-City	Hyogo
Japan	Novartis Investigative Site	Kochi city	Kochi
Japan	Novartis Investigative Site	Kumamoto-city	Kumamoto
Japan	Novartis Investigative Site	Kurume-city	Fukuoka
Japan	Novartis Investigative Site	Kurume-city	Fukuoka
Japan	Novartis Investigative Site	Kusatsu city	Shiga
Japan	Novartis Investigative Site	Kushiro-city	Hokkaido
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Mito-city	Ibaraki
Japan	Novartis Investigative Site	Musashino-city	Tokyo
Japan	Novartis Investigative Site	Nagakute-city	Aichi
Japan	Novartis Investigative Site	Nakano-city	Nagano
Japan	Novartis Investigative Site	Niigata-city	Niigata
Japan	Novartis Investigative Site	Ogaki-city	Gifu
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Saijo-city	Ehime
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Saku-city	Nagano
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sayama-city	Saitama
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Seto-city	Aichi
Japan	Novartis Investigative Site	Shinagawa ku	Tokyo
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Takamatsu city	Kagawa
Japan	Novartis Investigative Site	Tanabe-city	Wakayama
Japan	Novartis Investigative Site	Ueda-city	Nagano
Japan	Novartis Investigative Site	Uji-city	Kyoto
Japan	Novartis Investigative Site	Wako-city	Saitama
Japan	Novartis Investigative Site	Yatsushiro-city	Kumamoto
Japan	Novartis Investigative Site	Yokohama city	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Jordan	Novartis Investigative Site	Amman	JOR
Jordan	Novartis Investigative Site	Amman
Jordan	Novartis Investigative Site	Amman
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Cheongju si	Chungcheongbuk Do
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Gyeonggi do	Bucheon Si
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Wonju	Gangwon-do
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Hazmieh
Malaysia	Novartis Investigative Site	Kota Kinabalu	Sabah
Malaysia	Novartis Investigative Site	Kuala Lumpur	Selangor Darul Ehsan
Malaysia	Novartis Investigative Site	Kuala Lumpur	MYS
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Sungai Buloh	Selangor Darul Ehsan
Philippines	Novartis Investigative Site	Makati City
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Manila	Metro Manila
Philippines	Novartis Investigative Site	Pasig City
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Quezon City	Manila
Philippines	Novartis Investigative Site	San Juan City
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Kaohsiung City
Taiwan	Novartis Investigative Site	New Taipei
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Taiwan	Novartis Investigative Site	Yilan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Muang
Thailand	Novartis Investigative Site	Songkhla	Hat Yai

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  India,  Japan,  Jordan,  Korea, Republic of,  Lebanon,  Malaysia,  Philippines,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to WHF	Results are given in terms of number of participants with at least one worsening heart failure (WHF) event through day 5 (pre-defined timeframe).	Through Day 5
Secondary	Time to CV Death	analysis of time to CEC CV death through day 180 : results are given in terms of number of participants with CV death event through day 180 (pre-defined timeframe).	Through Day 180
Secondary	Time to All-cause Death	Results are given in terms of number of participants with all cause death event through day 180 (pre-defined timeframe).	Through Day 180
Secondary	Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days	Time to event is computed as the number of days from randomization to moderate or marked improvements in dyspnea by Likert scale	Through Day 5
Secondary	Dyspnea by VAS-AUC Changes	Change from baseline in Dyspena by VAS-AUC through Day 5, expressed in mm-hours	Through Day 5
Secondary	Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization	Length of stay will be defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day	Up to day 30
Secondary	Renal Dysfunction and Prevention of Worsening of Renal Function	number of participants with renal dysfunction or in-hospital worsening of renal function through Day 5	Through Day 5
Secondary	Time to Re-hospitalization Due to Heart Failure and Renal Impairment	Time to event is computed as the number of days from randomization to re-hospitalization due to Heart Failure and renal impairment	Through Day 180
Secondary	Time to CV Death or Re-hospitalization Due to Heart Failure/ Renal Failure	Results are given in terms of number of participants with CV death or at least one re-hospitalization due to Heart Failure through day 180 (pre-defined timeframe).	Through Day 180
Secondary	Time to In-hospital Worsening Heart Failure Through Day 5	Results are given in terms of number of participants with at least one in-hospital worsening heart failure through day 5 (pre-defined timeframe). In-hospital worsening heart failure is defined by symptoms only, signs only, and both symptoms and signs.	Through Day 5
Secondary	Use of Loop Diuretic and Vasoactive Agents	Number of patients reported with use of loop diuretic and vasoactive agents from randomization through Day 5	Through Day 5
Secondary	Change From Baseline in Cardio-renal Biomarkers		Day 2 and Day 5
Secondary	Number of Patients Reported With Total Adverse Events, Serious Adverse Events and Death.	To evaluate the safety and tolerability of intravenous serelaxin in AHF patients, number of patients with total adverse events, serious adverse events and death will be analyzed.	For the safety evaluation, all adverse events will be collected from signing of the informed consent form through Day 5 for non-serious AEs and through Day 14 for serious AEs.