Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02007720
• Date of registration: 20/11/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF RELAX-AHF-ASIA
• Scientific 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
• Date of first enrolment: March 12, 2014
• Target sample size: 876
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02007720
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

China, Hong Kong, India, Japan, Jordan, Korea, Republic of, Lebanon, Malaysia, Philippines, Singapore, Taiwan, Thailand

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acute Heart Failure

Intervention(s)

Drug: Serelaxin

Drug: Placebo

Other: Standard of CareTherapy

Primary Outcome(s)

Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change. [Time Frame: through day 5]

Secondary Outcome(s)

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.]

Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization [Time Frame: Up to day 30]

Dyspnea by VAS-AUC Changes [Time Frame: Through Day 5]

Time to In-hospital Worsening Heart Failure Through Day 5 [Time Frame: Through Day 5]

Time to CV Death [Time Frame: Through Day 180]

Time to CV Death or Re-hospitalization Due to Heart Failure/ Renal Failure [Time Frame: Through Day 180]

Time to WHF [Time Frame: Through Day 5]

Time to Re-hospitalization Due to Heart Failure and Renal Impairment [Time Frame: Through Day 180]

Use of Loop Diuretic and Vasoactive Agents [Time Frame: Through Day 5]

Change From Baseline in Cardio-renal Biomarkers [Time Frame: Day 2 and Day 5]

Renal Dysfunction and Prevention of Worsening of Renal Function [Time Frame: Through Day 5]

Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days [Time Frame: Through Day 5]

Time to All-cause Death [Time Frame: Through Day 180]

Secondary ID(s)

CRLX030A2302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 02/08/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02007720