Publications home of jama and the specialty journals of. Many ahf patients have preserved ejection fraction hfpef. Efficacy, safety and tolerability of serelaxin when added to. It follows an earlier trial which was able to show that serelaxin improved symptoms such as shortness of breath dyspnoea in ahf patients, but also failed on hard clinical endpoints including cardiovascular death or readmission to hospital for heart or renal failure. Relax ahf 2 was a multicenter, randomized, doubleblind, placebocontrolled, eventdriven trial of serelaxin in addition to standard care in patients with acute heart. In the relaxahf trial published in 20, patients with acute heart failure ahf treated with serelaxin, a recombinant form of human relaxin 2. Representativeness of relaxahf clinical trial population. Serelaxin, recombinant human relaxin2, for treatment of acute heart failure relax ahf. The study population included data on 196 770 admissions from both adhere registries. Aug 27, 2007 efficacy and safety of relaxin for the treatment of acute heart failure relax ahf the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Pdf effects of serelaxin in patients with acute heart failure.
Pdf effects of serelaxin in patients with acute heart. We examined 196 770 ahf admissions from the acute decompensated heart failure national registryunited states and acute decompensated heart failure national registryinternational registries. Novartis acute heart failure therapy misses two main endpoints the failure of novartis acute heart failure therapy serelaxin to hit its objectives in a second phase iii trial is somewhat embarrassing for the company, which has been talking up the programme in recent months. Effect of ularitide on cardiovascular mortality in acute. Serelaxin fails to meet primary endpoints in phase 3 relax. We characterized how representative relax ahf clinical trial enrollees were to those patients with ahf found in international registries. The relax ahf trial was an international, prospective, double blind, placebo controlled, phase iii study comparing treatment with 48 h of intravenous serelaxin vs. Patients hospitalized for ahf with systolic blood pressure sbp 125 mmhg, mildtomoderate renal impairment, and increased levels of nterminal probtype natriuretic peptide nt.
Serelaxin data judged incomplete as fda panel sends it. The firstinclass recombinant form of human hormone relaxin 2 reduced dyspnea in the relax ahf trial but questions about its mortality benefit remained the drug was subsequently shot down for. May 25, 20 whereas in relaxahf, serelaxintreated patients had 3 kg bodyweight loss at day 14 only 06 kg less than patients receiving placebo. In this report, we describe the effects of serelaxin on prespeci. Serelaxin in acute heart failure radcliffecardiology. Efficacy, safety and tolerability of serelaxin when added. The phase iii trial, relaxahf, has provided the strongest evidence to date of serelaxins efficacy in the treatment of ahf. This was a huge disappointment as we had such encouraging data from previous studies, said coprincipal investigator pi prof. Serelaxin has failed to meet the primary endpoints of the phase 3 relax ahf 2 trial, according to late breaking results presented for the first time today at heart failure 2017 and the 4th world congress on acute heart failure. In the relaxahf trial, consistent with the prerelaxahf phase ii study, the early administration of intravenous serelaxin was associated with a combined 38% decrease in 180day allcause mortality p 0.
To test how accurate the recently published relaxahf trial was in recruiting realworld patients with acutedecompensated heart failure adhf. The methods of the relaxahf trial nct00520806 are described in detail elsewhere. Relaxahf stirs interest in novel drug for acute heart failure. Effects of serelaxin in patients with acute heart failure nejm. Although the relaxahf trial demonstrated the efficacy of a novel therapy, serelaxin, in ahf, future studies will be necessary to evaluate the extent. Relaxahf was an international, doubleblind, placebocontrolled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned 1. The ahf patients randomized to either serelaxin or placebo in the study were followed for a period. The firstinclass recombinant form of human hormone relaxin 2 reduced dyspnea in the relaxahf trial but questions about its mortality benefit. Acute intravenous injection of serelaxin recombinant. Some pair relax ahf 2 with the recently disappointing true ahf trial of ularitide cardiorentis as the latest in an oftcited, notoriously long list of studies that similarly tested vasodilating.
Although trials enroll higher risk patients at baseline compared with registries, the trend is informative. Serelaxin has failed to meet the primary endpoints of the phase 3 relaxahf2 trial, according to late breaking results presented for the first time today at heart failure 2017 and the 4th world congress on acute heart failure. Relaxahf was a phase iii, multicenter, randomized, doubleblind, placebocontrolled study designed to investigate the efficacy and safety of serelaxin in the treatment of ahf 36, 37. Effect of serelaxin on mode of death in acute heart. Relationship between left ventricular ejection fraction. Our findings differ from those of the relaxahf trial, in which treatment with the vasodilator serelaxin at a median of 7 hours after clinical evaluation led to decreases in ntprobnp levels and. In the relaxahf trial published in 20, patients with acute heart failure ahf treated with serelaxin, a recombinant form of human relaxin 2, had a reduced incidence of worsening. Relaxahf trial also showed similar outcomes after serelaxin treatment. Jun 06, 20 the ahf patients randomized to either serelaxin or placebo in the study were followed for a period of 180 days, and were required to receive standardofcare background hf management during both the index hospitalization and post discharge according to regional or local guidelinesinstitutional standards.
Another acute heart failure drug fails in large clinical trial. In the relax ahf trial published in 20, patients with acute heart failure ahf treated with serelaxin, a recombinant form of human relaxin 2, had a reduced incidence of worsening. Use of highsensitivity troponin t to identify patients with. This paper was a subgroup analysis of the relaxahf ef. Effect of serelaxin on cardiac, renal, and hepatic biomarkers. Mode of death prevention by serelaxin we read with interest the article by felker et al. Representativeness of relaxahf clinical trial population in. Relief of breathlessness for serelaxin was the symptom targeted by the original relaxahf trial, which corthera began back in 2007. With the exception of the protect study, all other ahf trials excluded patients with hfpef table 1. Pdf serelaxin a novel treatment for acute heart failure. Relaxin in acute heart failure2 american college of cardiology. Nov 20, 2012 the phase iiiii relaxahf trial was conducted as a followup to the phase ii prerelaxahf study, which suggested that relaxin 30 gkg per day improved dyspnoea and clinical outcomes in the. Relaxahf randomized 1161 ahf patients to 48h serelaxin 30.
In the phase 3 relax ahf trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for ahf. Relax ahf trial also showed similar outcomes after serelaxin treatment. This phase iiib outcome study in ahf patients was designed as a multicenter, randomized, doubleblind, placebocontrolled, eventdriven study in order to assess the efficacy, safety and tolerability of intravenous infusion of serelaxin or placebo. The relaxin for the treatment of acute heart failure relax ahf trial enrolled 1161 patients admitted to the hospital for acute heart failure ahf to evaluate the therapeutic efficacy of serelaxin, a recombinant form of human relaxin2. In the relax ahf trial, intravenous iv serelaxin infusion was associated with an improvement in dyspnoea and a reduction in the risk of cardiovascular death at 6 months in patients hospitalized for acute heart failure ahf. Serelaxin, recombinant human relaxin2, for heart failure. May 01, 2017 serelaxin has failed to meet the primary endpoints of the phase 3 relax ahf 2 trial, according to late breaking results presented for the first time today at heart failure 2017 and the 4th world. Perhaps myocardial injury is a key pathophysiologic marker in the majority of patients with ahf. Backgrounda recent clinical trial relaxin in acute heart failure relaxahf demonstrated that 48 hours of continuous intravenous infusion of the vasorelaxant peptide serelaxin recombinant human relaxin2 to patients with acute heart failure reduced cardiovascular mortality at 180 days. In the relaxahf2 trial 6,600 patients hospitalized for acute heart failure were randomized to a 48hour infusion of serelaxin or placebo. Serelaxin treatment does not reduce incidence of death in. The relaxahf2 trial failed to show that serelaxin was superior to. This article is from european heart journal, volume 34. Relaxahf2 was a multicentre trial enrolling approximately 6 600 patients hospitalised for ahf.
Patients were randomised within 16 hours from presentation to 48hour intravenous infusions of serelaxin 30 gkgday or placebo, both in addition to standard of care. In the relaxahf trial, 1,161 patients were randomized to serelaxin or placebo in the first hours of acute decompensated heart failure. Novartis acute heart failure therapy misses two main endpoints the failure of novartis acute heart failure therapy serelaxin to hit its objectives in a second phase iii trial is somewhat embarrassing for the company, which. Acute heart failure remains an enormous health concern worldwide, and is a major cause of death and hospitalization. It significantly improved patients dyspnoea, resulted in a 30% reduction in worsening of heart. In the relaxahf trial published in 20, patients with acute heart failure ahf treated with serelaxin, a recombinant form of. As demonstrated in the revive ii trial,3 low sbp at baseline is associated with increased inhospital and postdischarge mortality and to avoid this adverse outcome, relax ahf enrolled a set of patients with a lower baseline risk. In this trial involving patients who were hospitalized for acute heart failure. We are committed to understanding serelaxins effects on rehospitalisation, beyond the confounding effects of the greater proportion of patients with a history of previous hospitalisation for heart failure, the shorter length of stay and the improved survival. Serelaxin treatment does not reduce incidence of death in patients. In relaxahf ejection fraction was available for most. Briefly, the relaxahf study was a doubleblind, prospective, multicenter clinical trial that randomized 1,161 patients within 16 h of ahf presentation to either intravenous serelaxin 30. This symptom was assessed by patients via the visual analogue scale vas to describe relief from breathlessness over five days, and a sevenpoint scale to capture changes in symptoms.
The project had previously shown promise in the smaller relaxahf trial enough at least for novartis to press on with the 6,500patient relaxahf2 study after initially being knocked back by the fda event novartis writing second act in heart failure, december 8, 2016. There was no significant difference between the two groups in either of the two primary endpoints, cardiovascular mortality at 180 days 8. Efficacy and safety of relaxin for the treatment of acute heart failure relaxahf the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Efficacy and safety of relaxin for the treatment of acute heart. Relationship between left ventricular ejection fraction and. Given the lack of evidencebased therapies in this population, we evaluated the effects of serelaxin according to ef in relaxahf trial. The recently published relaxahf efficacy and safety of relaxin for the treatment of acute heart failure study was a prospective, randomised, doubleblind, placebocontrolled trial carried out in a targeted population of patients with acute hf. Applying relaxahf inclusionexclusion criteria demonstrate that. Relax ahf was an international, doubleblind, placebocontrolled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned 1. In the phase 3 relaxahf trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for ahf.
The drug studied in relax ahf was serelaxin, a recombinant form of human relaxin2. Relaxahfasia, a multinational, randomised, doubleblind, placebocontrolled, phase iii trial, evaluated the effects of serelaxin on symptom relief and clinical. We compared clinical and outcome data of patients receiving serelaxin in the relaxahf trial relax group, n 581 with patients included in the eahfe registry 5497 adhf from 29 spanish emergency departments eds. Publications home of jama and the specialty journals of the. Serelaxin in acute heart failure patients with preserved. Relaxahf was generally similar in terms of the elements of study design compared with previous ahf trials, as shown in table 1. Some pair relaxahf2 with the recently disappointing trueahf trial of ularitide cardiorentis as the latest in an oftcited, notoriously long list of. In the phase 3 relaxahf trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients. Serelaxin, recombinant human relaxin2, for heart failure pa. In a post hoc exploratory analysis, we explored the association of these changes with 180day mortality in the relaxahf. The relaxahf trial was an international, prospective, double blind, placebo controlled, phase iii study comparing treatment with 48 h of intravenous serelaxin vs. Efficacy and safety of relaxin for the treatment of acute heart failure relax ahf the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Serelaxin in acute heart failure patients with preserved left.
Efficacy and safety of relaxin for the treatment of acute. May 05, 2017 in the relax ahf 2 trial 6,600 patients hospitalized for acute heart failure were randomized to a 48hour infusion of serelaxin or placebo. May 22, 2017 serelaxin failed to meet the primary endpoints of the phase 3 relaxahf2 trial, according to latebreaking results presented at heart failure 2017 and the 4th world congress on acute heart failure, april 29may 2 in paris, france. Compared to placebo, serelaxin also reduced worsening heart failure whf by 47% through day 5 and both allcause and cardiovascular mortality by 37% through day 180. The safety and scientific validity of this study is the responsibility of the. The design and primary results of the relaxahf study were published previously. Not time to relax in acute heart failure authors reply. What can we learn from relaxahf compared to previous ahf. Listing a study does not mean it has been evaluated by the u. We characterized how representative relaxahf clinical trial enrollees were to those. Effects of serelaxin in patients with acute heart failure. Serelaxin in addition to standard therapy in acute heart. Mar 28, 2014 relief of breathlessness for serelaxin was the symptom targeted by the original relax ahf trial, which corthera began back in 2007. Serelaxin data judged incomplete as fda panel sends it back.
Effect of serelaxin on mode of death in acute heart failure. In the relax ahf trial, consistent with the pre relax ahf phase ii study, the early administration of intravenous serelaxin was associated with a combined 38% decrease in 180day allcause mortality p 0. Patients hospitalized for acute heart failure ahf differ with respect of many clinical. In spite of this, the treatment strategies for acute. In phase iii the relaxahf trial gave a 48hr intravenous infusion of the same dose. Effect of serelaxin on cardiac, renal, and hepatic.
Vascular effects of serelaxin in patients with stable. A series of clinical trials have assessed indicators of dyspnea, which showed different results. In the relaxahf trial, intravenous iv serelaxin infusion was associated with an improvement in dyspnoea and a reduction in the risk of cardiovascular death at 6 months in patients hospitalized for acute heart failure ahf. The rationale for, and design of, the relax trial have been described. Serelaxin, recombinant human relaxin2, for heart failure patients. Serelaxin has failed to meet the primary endpoints of the phase 3 relaxahf2 trial, according to late breaking results presented for the first time. Efficacy and safety of relaxin for the treatment of acute heart failure relax ahf. Use of highsensitivity troponin t to identify patients. It had no effect on cardiac index and caused only a. Serelaxin, recombinant human relaxin2, for treatment of acute heart failure relaxahf. The relaxin for the treatment of acute heart failure relaxahf trial enrolled 1161 patients admitted to the hospital for acute heart failure ahf to evaluate the therapeutic efficacy of serelaxin, a recombinant form of human relaxin2. Relaxahf2 was a multicenter, randomized, doubleblind, placebocontrolled, eventdriven trial of serelaxin in addition to standard care in patients with acute heart.
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