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
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
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.
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:
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
Xian, Shanxi 710061, China
Rajasthan, India 334003, India
Chuo Ku, Tokyo 104-8560, Japan
Itabashi-ku, Tokyo 173-8610, Japan
Shinagawa Ku, Tokyo 141 8625, Japan
Shinagawa-ku, Tokyo 142-8666, Japan
Kuala Lumpur, Selangor 43000, Malaysia
Bundang Gu, Gyeonggi-do 13620, South Korea
Muang, 40002, Thailand