Acute Heart Failure
Conditions
Interventions
investigational material(s)
Generic name etc : RLX030
INN of investigational material : Serelaxin
Therapeutic category code : 219 Other cardiovascular agents
Dosage and Administration for Investigatio
Sponsors
Novartis Pharma K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Male or female>= 18 years of age, with body weight = 350 pg/mL or NT-proBNP >= 1,400 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 -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
Exclusion criteria: -Dyspnea primarily due to non-cardiac causes -Temperature more than 38.5C (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 -AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate less than 45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of more than 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 more than 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 less than 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with a clinical composite endpoint of treatment success, treatment failure, or no change. [ Time Frame: Treatment success at Day 2, Treatment failure through Day 5, and No change through Day 5 ] [ Designated as safety issue: No ] 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to Worsening Heart Failure [ Time Frame: Through Day 5 ] [ Designated as safety issue: No ] Time to event is computed as the number of days from randomization to Worsening Heart Failure Time to cardiovascular death [ Time Frame: Through Day 180 ] [ Designated as safety issue: No ] Time to event is computed as the number of days from randomization to cardiovascular death Time to all-cause death [ Time Frame: Through Day 180 ] [ Designated as safety issue: No ] Time to event is computed as the number of days from randomization to all cause death Time to moderate or marked improvements in dyspnea by Likert scale [ Time Frame: Through Day 5 ] [ Designated as safety issue: No ] Time to event is computed as the number of days from randomization to moderate or marked improvements in dyspnea by Likert scale Dyspnea by VAS-AUC changes [ Time Frame: Through Day 5 ] [ Designated as safety issue: No ] Change from baseline in Dyspena by VAS-AUC through Day 5 Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) stay for the index AHF hospitalization [ Time Frame: Up to day 30 ] [ Designated as safety issue: No ] Length of stay will be defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day Renal dysfunction and prevention of worsening of renal function [ Time Frame: Through Day 5 ] [ Designated as safety issue: No ] Time to re-hospitalization due to Heart Failure and renal impairment [ Time Frame: Through Day 180 ] [ Designated as safety issue: No ] Time to event is computed as the number of days from randomization to re-hospitalization due to Heart Failure and renal impairment Time to CV death or re-hospitalization due to Heart Failure/ Renal Failure [ Time Frame: Through Day 180 ] [ Designated as safety issue: No ] Time to event is computed as the number of days from randomization to CV death or re-hospitalization due to Heart Failure Use of loop diuretic and vasoactive agents [ Time Frame: Through Day 5 ] [ De | — |
Outcome results
None listed