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NCT02064868: RELAX-AHF-EU

Effect of Serelaxin Versus Standard of Care in Acute Heart Failure (AHF) Patients

Terminated Phase 3 Results posted Last updated 22 March 2019
What this trial tests

Phase 3 trial testing Serelaxin in Acute Heart Failure (AHF) in 2,666 participants. Terminated before completion.

Timeline
31 January 2014
Primary endpoint
26 March 2017
25 April 2017

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment2,666
Start date31 January 2014
Primary completion26 March 2017
Estimated completion25 April 2017
Sites357 locations across Italy, Finland, Poland, Croatia, Russia, Belgium, Estonia, Lithuania

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Acute Heart Failure (AHF). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Worsening Heart Failure (WHF) / All Cause of Deaths Through Day 5 Primary · 5 days

In-hospital WHF through Day 5 post-randomization included worsening signs and/or symptoms of heart failure that required an intensification of intravenous therapy for heart failure or mechanical ventilation, renal or circulatory support. A central event adjudication committee was appointed to oversee the WHF primary endpoint adjudication.

GroupValue95% CI
Serelaxin + Standard of Care4.95
Standard of Care (SOC)6.94
Percentage of Participants With In-hospital Worsening Heart Failure/All-Cause Death/Readmission for Heart Failure Through Day 14 Secondary · 14 days

WHF/death/readmission for heart failure through Day 14. WHF/deaths through Day 5 were adjudicated and confirmed by the Clinical Endpoint Committee, WHF/deaths after Day 5 through Day 14 and readmission through Day 14 were as reported by the investigators.

GroupValue95% CI
Serelaxin + Standard of Care8.49
Standard of Care (SOC)10.63
Percentage of Participants With Persistent Sign or Symptoms of Heart Failure / Non-Improvement at Any Post Baseline Visit Through Day 5 Secondary · 5 days

Persistent or non-improvement in any signs or symptoms of HF at any post baseline visit up to Day 5.

GroupValue95% CI
Serelaxin + Standard of Care8684 – 87
Standard of Care (SOC)9189 – 93
Percentage of Participants With Renal Deterioration at Any Post Baseline Visit Through Day 14 Secondary · 14 days

Renal deterioration is defined as \> or = 0.3 mg/dL increase from screening in serum creatinine.

GroupValue95% CI
Serelaxin + Standard of Care3634 – 38
Standard of Care (SOC)4440 – 47
Length of Index Hospital Stay Secondary · 30 Days

Length of stay (in hours) is defined as the index hospitalization discharge date and time minus the index hospitalization start date and time.

GroupValue95% CI
Serelaxin + Standard of Care251.28± 162.368
Standard of Care (SOC)243.59± 160.270
Percentage of Participants With Adverse Events as Assessment of Safety and Tolerability of Serelaxin in AHF Patients Secondary · Adverse Events (AE): 5 Days / Serious Adverse Events (SAE): 14 days / All cause deaths 30 days
Patients with any AE through Day 5
GroupValue95% CI
Serelaxin + Standard of Care58.13
Standard of Care (SOC)56.04
Patients with any SAE through Day 14
GroupValue95% CI
Serelaxin + Standard of Care12.38
Standard of Care (SOC)11.97
All cause deaths through Day 5
GroupValue95% CI
Serelaxin + Standard of Care0.58
Standard of Care (SOC)0.67
All cause deaths through Day 14
GroupValue95% CI
Serelaxin + Standard of Care1.91
Standard of Care (SOC)2.01
All cause deaths through Day 30
GroupValue95% CI
Serelaxin + Standard of Care3.30
Standard of Care (SOC)4.25
Change From Baseline in Health-related Quality of Life Index Value, Assessed by EuroQoL EQ-5D-5L Questionnaire. Secondary · Baseline, Day 5, Day 14

EQ-5D-5L is a questionnaire designed to assess health status in adults consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The results were converted into a single index value using UK as the reference country for all countries. Range -0.3 (worst possible state) to 1 (best possible state).

Day 5
GroupValue95% CI
Serelaxin + Standard of Care0.28± 0.298
Standard of Care (SOC)0.27± 0.292
Day 14
GroupValue95% CI
Serelaxin + Standard of Care0.32± 0.328
Standard of Care (SOC)0.31± 0.317

Adverse events — posted to ClinicalTrials.gov

Time frame: All Cause Mortality: 30 days (additional deaths are included which occurred after the clinical trial reporting period of 30 days for up to 8 months post randomization); Serious Adverse Events: 14 days; Other non-serious Adverse Events (AEs): 5 days. Reporting threshold: 1.5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Serelaxin + Standard of Care
Serious: 214/1729 (12%)
Deaths: 63/1729
Standard of Care (SOC)
Serious: 107/894 (12%)
Deaths: 43/894

Serious adverse events (187 terms)

ReactionSystemSerelaxin + Standard of CareStandard of Care (SOC)
Cardiac failureCardiac disorders
PneumoniaInfections and infestations
Acute kidney injuryRenal and urinary disorders
BradycardiaCardiac disorders
Coronary artery diseaseCardiac disorders
HypotensionVascular disorders
Acute myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failure acuteCardiac disorders
Renal failureRenal and urinary disorders
Acute pulmonary oedemaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Mitral valve incompetenceCardiac disorders
Ventricular fibrillationCardiac disorders
Ventricular tachycardiaCardiac disorders
Renal impairmentRenal and urinary disorders
Angina unstableCardiac disorders
PyrexiaGeneral disorders
Urinary tract infectionInfections and infestations
Ischaemic strokeNervous system disorders
Aortic valve stenosisCardiac disorders
Atrioventricular block completeCardiac disorders
Cardiogenic shockCardiac disorders
Myocardial infarctionCardiac disorders
Other adverse events (21 terms — click to expand)

ReactionSystemSerelaxin + Standard of CareStandard of Care (SOC)
HypokalaemiaMetabolism and nutrition disorders
Cardiac failureCardiac disorders
ConstipationGastrointestinal disorders
InsomniaPsychiatric disorders
Urinary tract infectionInfections and infestations
AnaemiaBlood and lymphatic system disorders
Blood pressure systolic decreasedInvestigations
HypotensionVascular disorders
HyperuricaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
Atrial fibrillationCardiac disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Renal impairmentRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
Mitral valve incompetenceCardiac disorders
Back painMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
PyrexiaGeneral disorders
BronchitisInfections and infestations
Renal failureRenal and urinary disorders

Most-reported serious reactions: Cardiac failure, Pneumonia, Acute kidney injury, Bradycardia, Coronary artery disease, Hypotension, Acute myocardial infarction, Atrial fibrillation.

Data from ClinicalTrials.gov NCT02064868 adverse events section.

Sponsor's own description

This was a multinational, multicenter, randomized, open-label study to confirm and expand the efficacy, safety and tolerability evidence of 48 hours intravenous infusion of serelaxin (30 micrograms/kg/day) when added to Standard of Care (SoC) in patients admitted to hospital for Acute Heart Failure (AHF).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Novel Anti-fibrotic Therapies.
    McVicker BL, Bennett RG. · · 2017 · cited 50× · PMID 28620300 · DOI 10.3389/fphar.2017.00318
  2. G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention.
    Conrad KP. · · 2016 · cited 30× · PMID 27385360 · DOI 10.1093/humupd/dmw021
  3. Heart failure-potential new targets for therapy.
    Nabeebaccus A, Zheng S, Shah AM. · · 2016 · cited 24× · PMID 27365454 · DOI 10.1093/bmb/ldw025
  4. Synthetic non-peptide low molecular weight agonists of the relaxin receptor 1.
    Agoulnik AI, Agoulnik IU, Hu X, Marugan J. · · 2017 · cited 19× · PMID 27771940 · DOI 10.1111/bph.13656
  5. Systolic Blood Pressure and Outcome in Patients Admitted With Acute Heart Failure: An Analysis of Individual Patient Data From 4 Randomized Clinical Trials.
    Grand J, Miger K, Sajadieh A, Køber L, et al · · 2021 · cited 11× · PMID 34514815 · DOI 10.1161/jaha.121.022288
  6. Cardiovascular effects of relaxin-2: therapeutic potential and future perspectives.
    Almeida-Pinto N, Dschietzig TB, Brás-Silva C, Adão R. · · 2024 · cited 6× · PMID 37721595 · DOI 10.1007/s00392-023-02305-1
  7. Blood Pressure Drops During Hospitalization for Acute Heart Failure Treated With Serelaxin: A Patient-Level Analysis of 4 Randomized Controlled Trials.
    Grand J, Miger K, Sajadieh A, Køber L, et al · · 2022 · cited 4× · PMID 35184572 · DOI 10.1161/circheartfailure.121.009199

Verify or expand the search:

Other trials of Serelaxin

Trials testing the same drug.

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Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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