Clinical Trials List
Protocol NumberCRLX030A2302
NCT Number(ClinicalTrials.gov Identfier)NCT02007720
2014-05-01 - 2019-03-31
Phase III
Terminated10
ICD-10I50.9
Heart failure, unspecified
ICD-10I51.9
Heart disease, unspecified
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
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 王宇澄 Division of Cardiovascular Diseases
- 盧炯睿 Division of Cardiovascular Diseases
- 林晏年 Division of Cardiovascular Diseases
- Ping-Han Lo Division of Cardiovascular Diseases
- Po-Yen Ko Division of Cardiovascular Diseases
- Pei-Ying Pai Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Hao-min Cheng Division of Cardiovascular Diseases
- 黃少嵩 Division of Cardiovascular Diseases
- 許百豐 Division of Cardiovascular Diseases
- Shih-Hsien Sung Division of Cardiovascular Diseases
- Po-Hsun Huang Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- YEN-HUNG LIN Division of General Internal Medicine
- 林柏志 Division of General Internal Medicine
- 張博淵 Division of General Internal Medicine
- WEI-TIEN CHANG Division of General Internal Medicine
- CHO-KAI WU Division of General Internal Medicine
- 賀立婷 Division of General Internal Medicine
- JYH-MING JIMMY JUANG Division of General Internal Medicine
- Chih-Fan Yeh Division of General Internal Medicine
- CHIEN-HUA HUANG Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 鄭凱鴻 Division of Cardiovascular Diseases
- 朱志生 Division of Cardiovascular Diseases
- Chun-Yuan Chu Division of Cardiovascular Diseases
- Tsung-Hsien Lin Division of Cardiovascular Diseases
- 顏學偉 Division of Cardiovascular Diseases
- 溫文才 Division of Cardiovascular Diseases
- Ye-Hsu Lu Division of Cardiovascular Diseases
- Cheng-An Chiu Division of Cardiovascular Diseases
- Po-Chao Hsu Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Po-Sheng Chen Division of General Internal Medicine
- Yen-Wen Liu Division of General Internal Medicine
- 李文煌 Division of General Internal Medicine
- 黃成偉 Division of General Internal Medicine
- Ping-Yen Liu Division of General Internal Medicine
- Yi-Heng Li Division of General Internal Medicine
- Ju-Yi Chen Division of General Internal Medicine
- Wei-Chuan Tsai Division of General Internal Medicine
- 林志展 Division of General Internal Medicine
- Ting-Hsing Chao Division of General Internal Medicine
- 李貽恆 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Acute Heart Failure Patients
Objectives
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.
Test Drug
REASANZ
Active Ingredient
Serelaxin
Dosage Form
Concentrate for Solution for Infusion
Dosage
3.5
Endpoints
Primary Outcome Measures :
Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change. [ Time Frame: through day 5 ]
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 Outcome Measures :
Time to WHF [ Time Frame: Through Day 5 ]
Results are given in terms of number of participants with at least one worsening heart failure (WHF) event through day 5 (pre-defined timeframe).
Time to CV Death [ Time Frame: Through Day 180 ]
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).
Time to All-cause Death [ Time Frame: Through Day 180 ]
Results are given in terms of number of participants with all cause death event through day 180 (pre-defined timeframe).
Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days [ Time Frame: Through Day 5 ]
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 ]
Change from baseline in Dyspena by VAS-AUC through Day 5, expressed in mm-hours
Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization [ Time Frame: Up to day 30 ]
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 ]
number of participants with renal dysfunction or in-hospital worsening of renal function through Day 5
Time to Re-hospitalization Due to Heart Failure and Renal Impairment [ Time Frame: Through Day 180 ]
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 ]
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).
Time to In-hospital Worsening Heart Failure Through Day 5 [ Time Frame: 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.
Use of Loop Diuretic and Vasoactive Agents [ Time Frame: Through Day 5 ]
Number of patients reported with use of loop diuretic and vasoactive agents from randomization through Day 5
Change From Baseline in Cardio-renal Biomarkers [ Time Frame: Day 2 and Day 5 ]
Number of Patients Reported With Total Adverse Events, Serious Adverse Events and Death. [ 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. ]
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.
Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change. [ Time Frame: through day 5 ]
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 Outcome Measures :
Time to WHF [ Time Frame: Through Day 5 ]
Results are given in terms of number of participants with at least one worsening heart failure (WHF) event through day 5 (pre-defined timeframe).
Time to CV Death [ Time Frame: Through Day 180 ]
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).
Time to All-cause Death [ Time Frame: Through Day 180 ]
Results are given in terms of number of participants with all cause death event through day 180 (pre-defined timeframe).
Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days [ Time Frame: Through Day 5 ]
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 ]
Change from baseline in Dyspena by VAS-AUC through Day 5, expressed in mm-hours
Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization [ Time Frame: Up to day 30 ]
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 ]
number of participants with renal dysfunction or in-hospital worsening of renal function through Day 5
Time to Re-hospitalization Due to Heart Failure and Renal Impairment [ Time Frame: Through Day 180 ]
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 ]
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).
Time to In-hospital Worsening Heart Failure Through Day 5 [ Time Frame: 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.
Use of Loop Diuretic and Vasoactive Agents [ Time Frame: Through Day 5 ]
Number of patients reported with use of loop diuretic and vasoactive agents from randomization through Day 5
Change From Baseline in Cardio-renal Biomarkers [ Time Frame: Day 2 and Day 5 ]
Number of Patients Reported With Total Adverse Events, Serious Adverse Events and Death. [ 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. ]
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.
Inclution 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).
Exclusion Criteria
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
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
The Estimated Number of Participants
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Taiwan
96 participants
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Global
1520 participants
