Clinical trial NCT02007720: Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Heart Failure
Keywords: Serelaxin,
WHF,
Likert Scale,
RELAX-AHF-ASIA,
RLX030,
AHF,
acute heart failure
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-12-11
Enrollment: 876
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change.
timeFrame: through day 5
Secondary outcomes:
measure: Time to WHF
timeFrame: Through Day 5
measure: Time to CV Death
timeFrame: Through Day 180
measure: Time to All-cause Death
timeFrame: Through Day 180
measure: Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days
timeFrame: Through Day 5
measure: Dyspnea by VAS-AUC Changes
timeFrame: Through Day 5
measure: Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization
timeFrame: Up to day 30
measure: Renal Dysfunction and Prevention of Worsening of Renal Function
timeFrame: Through Day 5
measure: Time to Re-hospitalization Due to Heart Failure and Renal Impairment
timeFrame: Through Day 180
measure: Time to CV Death or Re-hospitalization Due to Heart Failure/ Renal Failure
timeFrame: Through Day 180
measure: Time to In-hospital Worsening Heart Failure Through Day 5
timeFrame: Through Day 5
measure: Use of Loop Diuretic and Vasoactive Agents
timeFrame: Through Day 5
measure: Change From Baseline in Cardio-renal Biomarkers
timeFrame: Day 2 and Day 5
measure: Number of Patients Reported With Total Adverse Events, Serious Adverse Events and Death.
timeFrame: 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.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Lanzhou
country: China
facility: Novartis Investigative Site
state: Gansu
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Yangzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Jinshan
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Wenzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Shanghai City
country: China
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Vadodara
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Rajasthan
country: India
facility: Novartis Investigative Site
city: Nagakute-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Seto-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kamogawa-city
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Saijo-city
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Chikushino-city
country: Japan
facility: Novartis Investigative Site
state: Fukuka
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Iizuka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kurume-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kurume-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Ogaki-city
country: Japan
facility: Novartis Investigative Site
state: Gifu
city: Kushiro-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Amagasaki city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kobe-City
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Mito-city
country: Japan
facility: Novartis Investigative Site
state: Ibaraki
city: Kanazawa
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Kanonji-city
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Takamatsu city
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Kawasaki-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kochi city
country: Japan
facility: Novartis Investigative Site
state: Kochi
city: Kumamoto-city
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Yatsushiro-city
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Kyoto-city
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Uji-city
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Sendai-city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Nakano-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Saku-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Ueda-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Niigata-city
country: Japan
facility: Novartis Investigative Site
state: Niigata
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kawaguchi-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Sayama-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Wako-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Kusatsu city
country: Japan
facility: Novartis Investigative Site
state: Shiga
city: Hamamatsu-city
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Kakegawa-city
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Akishima-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hachioji-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Musashino-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Tanabe-city
country: Japan
facility: Novartis Investigative Site
state: Wakayama
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Saitama
country: Japan
facility: Novartis Investigative Site
city: Amman
country: Jordan
facility: Novartis Investigative Site
state: JOR
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Gyeonggi do
country: Korea, Republic of
facility: Novartis Investigative Site
state: Bucheon Si
city: Cheongju si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Chungcheongbuk Do
city: Wonju
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gangwon-do
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Incheon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Hazmieh
country: Lebanon
facility: Novartis Investigative Site
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: MYS
city: Kota Kinabalu
country: Malaysia
facility: Novartis Investigative Site
state: Sabah
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Selangor Darul Ehsan
city: Sungai Buloh
country: Malaysia
facility: Novartis Investigative Site
state: Selangor Darul Ehsan
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
state: Manila
city: Manila
country: Philippines
facility: Novartis Investigative Site
state: Metro Manila
city: Makati City
country: Philippines
facility: Novartis Investigative Site
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Pasig City
country: Philippines
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
city: San Juan City
country: Philippines
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Changhua
country: Taiwan
facility: Novartis Investigative Site
city: Kaohsiung City
country: Taiwan
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: New Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Yilan
country: Taiwan
facility: Novartis Investigative Site
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Muang
country: Thailand
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.