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.
Brief Title
Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Heart Failure
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
* 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
Inclusion 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).
* 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).
Gender
All
Gender Based
false
Keywords
Serelaxin,
WHF,
Likert Scale,
RELAX-AHF-ASIA,
RLX030,
AHF,
acute heart failure
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02007720
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CRLX030A2302
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change.
Outcome Time Frame
through day 5
Secondary Outcomes
Outcome Description
Results are given in terms of number of participants with at least one worsening heart failure (WHF) event through day 5 (pre-defined timeframe).
Outcome Time Frame
Through Day 5
Outcome Measure
Time to WHF
Outcome Description
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).
Outcome Time Frame
Through Day 180
Outcome Measure
Time to CV Death
Outcome Description
Results are given in terms of number of participants with all cause death event through day 180 (pre-defined timeframe).
Outcome Time Frame
Through Day 180
Outcome Measure
Time to All-cause Death
Outcome Description
Time to event is computed as the number of days from randomization to moderate or marked improvements in dyspnea by Likert scale
Outcome Time Frame
Through Day 5
Outcome Measure
Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days
Outcome Description
Change from baseline in Dyspena by VAS-AUC through Day 5, expressed in mm-hours
Outcome Time Frame
Through Day 5
Outcome Measure
Dyspnea by VAS-AUC Changes
Outcome Description
Length of stay will be defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day
Outcome Time Frame
Up to day 30
Outcome Measure
Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization
Outcome Description
number of participants with renal dysfunction or in-hospital worsening of renal function through Day 5
Outcome Time Frame
Through Day 5
Outcome Measure
Renal Dysfunction and Prevention of Worsening of Renal Function
Outcome Description
Time to event is computed as the number of days from randomization to re-hospitalization due to Heart Failure and renal impairment
Outcome Time Frame
Through Day 180
Outcome Measure
Time to Re-hospitalization Due to Heart Failure and Renal Impairment
Outcome Description
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).
Outcome Time Frame
Through Day 180
Outcome Measure
Time to CV Death or Re-hospitalization Due to Heart Failure/ Renal Failure
Outcome Description
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.
Outcome Time Frame
Through Day 5
Outcome Measure
Time to In-hospital Worsening Heart Failure Through Day 5
Outcome Description
Number of patients reported with use of loop diuretic and vasoactive agents from randomization through Day 5
Outcome Time Frame
Through Day 5
Outcome Measure
Use of Loop Diuretic and Vasoactive Agents
Outcome Time Frame
Day 2 and Day 5
Outcome Measure
Change From Baseline in Cardio-renal Biomarkers
Outcome Description
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.
Outcome Time Frame
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.
Outcome Measure
Number of Patients Reported With Total Adverse Events, Serious Adverse Events and Death.
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
James Tauras
Investigator Email
jtauras@montefiore.org
Investigator Phone
MeSH Terms
SERELAXIN PROTEIN, HUMAN
COUNTERFEIT DRUGS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS