Serelaxin
The pregnancy hormone made as a drug for acute heart failure, and why the large trial that was meant to confirm it came back flat
Serelaxin is a manufactured copy of relaxin-2, the hormone that widens blood vessels and raises kidney blood flow during pregnancy. Novartis gave it as a 48-hour drip to people admitted with acute heart failure. The first phase 3 trial, RELAX-AHF, eased breathlessness and hinted at fewer deaths; the much larger RELAX-AHF-2 found no effect on death or on early worsening of heart failure. The European regulator refused it in 2014, it was never approved in the US, and development stopped.
Used in human trials: 30 µg/kg per day, Continuous infusion, Intravenous (Phase 3: acute heart failure, 6,545 patients (RELAX-AHF-2)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Relaxin-2 is a peptide hormone best known from pregnancy, when it helps the mother's circulation adapt: blood vessels relax, the kidneys receive more blood and filter more. Serelaxin is that same hormone made by recombinant methods, two short chains held together by disulfide bridges, and it acts on the relaxin receptor RXFP1. The idea behind it was simple. People admitted to hospital with acute heart failure are congested and short of breath, their kidneys often struggle, and many die in the months after discharge. A drug that widened vessels and protected the heart and kidneys for a couple of days might ease the crisis and leave less lasting damage.
The first large test, RELAX-AHF, randomised 1,161 patients to a 48-hour infusion or placebo. Serelaxin improved one of its two breathlessness measures but not the other, and it did not change the combined rate of cardiovascular death or readmission at 60 days. What drew attention was a prespecified extra result: fewer deaths by day 180, 42 against 65. That signal was not a primary end point, and the trial was not built to prove it, so a second trial was designed to confirm it.
RELAX-AHF-2 enrolled 6,545 patients with the same 48-hour dose. Deaths from cardiovascular causes at 180 days were almost identical in the two groups, 8.7% on serelaxin and 8.9% on placebo, and worsening heart failure by day 5 was not significantly reduced. Hospital stay, all-cause death and readmissions did not differ either. An open-label European study, RELAX-AHF-EU, did report fewer early worsening events, but it was stopped early once RELAX-AHF-2 came back neutral, and its open design makes its result weaker. A sponsor-led pooled analysis of six trials found less early worsening and a modest overall mortality difference; an independent meta-analysis found no effect on mortality or breathlessness.
Serelaxin did do measurable things to the body. In smaller trials it lowered wedge and pulmonary artery pressures, raised kidney plasma flow, lowered blood pressure, and reduced blood markers of heart and kidney injury. A later analysis of RELAX-AHF-2 showed that these kidney improvements did not translate into fewer deaths or readmissions, which is one of the lessons the program left: a better lab value in the first two days did not mean a better outcome at six months.
Outside heart failure, small trials in cirrhosis tested it as a kidney vasodilator; it raised renal artery blood flow in one study but did not lower portal pressure in another, which ended early when the maker stopped supplying the drug. Europe's medicines committee refused authorisation in January 2014 and confirmed the refusal on re-examination in May 2014. There is no FDA record for it. Serelaxin is now a closed chapter, cited mainly as a well-run program whose early promise did not hold up.
Mechanism of Action
Serelaxin binds the same receptor as the body's own relaxin-2 and reproduces its effects on vessels and kidneys; the trials measured those effects well, but they did not add up to longer survival.
Vessel widening
Through RXFP1 it relaxes resistance vessels, lowering blood pressure and the filling pressures of the heart during an infusion (PMIDs 24255129, 32065620).
Kidney blood flow
It raised renal plasma flow in chronic heart failure and renal artery flow in cirrhosis, mirroring the kidney changes of pregnancy (PMIDs 25286914, 28245243).
Lower injury markers
Troponin, creatinine, cystatin C and NT-proBNP fell more than on placebo in the first days, but these changes did not predict fewer deaths (PMIDs 39663924, 36656377).
Anti-fibrotic in the lab
Relaxin opposes scar-forming signalling in cell and animal studies; clinical trials in fibrosis were inconclusive (PMID 33687895).
Published Research
These are studies in which serelaxin itself was given, read from their PubMed abstracts: the RELAX-AHF and RELAX-AHF-2 trials and their sub-analyses, the open-label European study, mechanistic trials of blood pressure, kidney and heart haemodynamics, pharmacokinetic studies, small trials in cirrhosis, two meta-analyses and a review.
RELAX-AHF-2: no effect on death or early worsening
In 6,545 patients admitted with acute heart failure and randomised within 16 hours to a 48-hour infusion or placebo, cardiovascular death by day 180 occurred in 8.7% on serelaxin and 8.9% on placebo, and worsening heart failure by day 5 in 6.9% and 7.7%; neither difference was significant. All-cause death, readmission and length of stay also did not differ, and adverse events were similar.
RELAX-AHF: some breathlessness relief, a mortality signal
Among 1,161 patients, serelaxin improved the visual-analogue breathlessness score but not the Likert breathlessness measure, and did not change cardiovascular death or readmission at 60 days or days alive out of hospital. A prespecified additional end point showed fewer deaths by day 180 (42 against 65), which the later RELAX-AHF-2 trial did not confirm.
Which deaths differed in RELAX-AHF
Of the 107 deaths by day 180 in RELAX-AHF, the lower count on serelaxin came mainly from other cardiovascular causes and, less certainly, sudden death; deaths from heart failure itself and from non-cardiovascular causes showed no apparent difference between groups.
RELAX-AHF-EU: an open-label study stopped early
This European study randomised 2,666 patients (of 3,183 planned) 2:1 to serelaxin added to usual care or usual care alone, without placebo, before the sponsor stopped it after RELAX-AHF-2. Adjudicated worsening heart failure or death by day 5 fell from 6.9% to 5.0%, but not at day 14; low blood pressure and falls in haemoglobin were more frequent with serelaxin.
Injury markers fell, deaths did not
In a 1,020-patient biomarker substudy of RELAX-AHF-2, serelaxin blunted the rise in troponin T over 14 days and lowered creatinine, cystatin C and uric acid at day 2, and NT-proBNP fell further. Cardiovascular death at 180 days was not reduced in this subgroup, though early worsening heart failure was.
Better kidney numbers did not explain outcomes
Analysing 6,318 RELAX-AHF-2 patients, the authors found serelaxin made an early improvement in kidney function more likely and a decline less likely, but the improvement did not carry through to death or readmission, so it did not mediate any treatment effect; they caution against using kidney function as a surrogate in future relaxin trials.
Lower filling pressures during the infusion
In 71 patients with acute heart failure and a high wedge pressure, a 20-hour infusion lowered peak pulmonary capillary wedge pressure by about 2.4 mmHg more than placebo in the first 8 hours and lowered pulmonary artery pressure throughout, with smaller falls in right atrial pressure and vascular resistance; cardiac index did not change.
More kidney blood flow in chronic heart failure
In 65 analysed patients with stable chronic heart failure and reduced kidney function, a 24-hour infusion raised renal plasma flow by 29% against 14% on placebo, without a difference in glomerular filtration rate; adverse events were similar between groups.
Blood pressure fell, heart perfusion unchanged
In 58 people with stable coronary artery disease given a 48-hour infusion or placebo, systolic pressure fell by roughly 10 to 13 mmHg more than placebo in the first 6 hours, but myocardial perfusion reserve on cardiac MRI and arterial stiffness did not change; serious adverse events over 180 days were similar.
Japanese phase 2 in acute heart failure
In 46 Japanese patients with acute heart failure given one of two infusion rates or placebo for up to 48 hours, adverse events were comparable across groups, serum levels rose with dose, and NT-proBNP fell by about half by day 2 on serelaxin.
Healthy-volunteer pharmacokinetics
In 32 healthy Japanese and 8 Caucasian volunteers given 48-hour infusions at three rates, serum levels climbed quickly, neared steady state within about 4 hours and dropped soon after the infusion ended; exposure was proportional to dose, filtration rate rose briefly, and kinetics were similar in both groups.
Liver impairment does not change exposure
In 49 people, 25 of them with mild to severe liver impairment, a single 24-hour infusion reached steady state at 12 to 24 hours and then declined with a mean terminal half-life of 7 to 8 hours; exposure matched healthy controls, no serious adverse events occurred and no antibodies to the drug developed.
Population pharmacokinetics across nine studies
Modelling data from 613 people in nine phase 1 and 2 studies, the authors fitted a three-compartment model; people with heart failure had a larger volume of distribution but similar clearance, and body mass index and kidney function shifted clearance only modestly, too little to matter clinically.
Kidney blood flow in cirrhosis
After work in two rat models of cirrhosis, 40 patients with alcohol-related cirrhosis were randomised to a two-hour serelaxin infusion or a single dose of terlipressin. Serelaxin raised total renal artery blood flow by 65% from baseline without lowering blood pressure or liver perfusion; the authors call it exploratory, in a small and stable group.
No fall in portal pressure (STOPP)
In a small phase 2 trial of cirrhosis with portal hypertension, 11 participants completed (9 on serelaxin); the hepatic venous pressure gradient did not change after two hours of infusion, and the trial ended early because the manufacturer discontinued the drug. There were no serious adverse events.
Pooled analysis of six acute heart failure trials
Pooling six randomised trials with 6,105 patients on serelaxin and 5,254 controls, this analysis by trial investigators found less worsening heart failure to day 5 (6.0% vs 8.1%) and a modest all-cause mortality difference at last follow-up (hazard ratio 0.87), but no effect on cardiovascular death, readmission or length of stay.
Independent meta-analysis: no mortality benefit
Across eight randomised trials with 8,477 participants, this meta-analysis concluded that serelaxin had no effect on 30-, 60- or 180-day mortality and did not improve breathlessness, although the pooled odds ratio it prints (0.79, interval 0.65 to 0.96) does not match that conclusion. Its abstract also calls the drug licensed for heart failure, which the regulatory records read for this page do not support.
Anti-fibrotic hopes, inconclusive trials
This review sets out how relaxin dampens TGF-beta1 signalling and myofibroblast activity in cell and animal work, then notes that every clinical trial of relaxin in fibrotic disease gave inconclusive results, and suggests where analogues might still be tested.
Dosing Data
Serelaxin was never approved, so there is no label dose. These are the infusion rates stated in the abstracts of published human studies; almost every trial used the same 48-hour schedule.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no regulator's label that says in what form Serelaxin is supplied. It is prepared and given by clinical staff, not bought and mixed at home: the next part says where.
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Serelaxin is prepared and given by clinical staff, in hospital, for acute heart failure.
In the carded trials it ran as a 48-hour infusion into a vein in patients admitted with acute heart failure.
Source: PMID 31433919 and PMID 23141816 (studies carded under Research below).
Storage before and after mixing
Unknown: no label on file says how Serelaxin is stored. It is kept and prepared by the hospital or clinic that gives it (see the part above); the home rules for a mixed vial in the mixing guide do not apply to it.
How it is taken
As it was given in human studies: Intravenous (Continuous infusion; Phase 3: acute heart failure, 6,545 patients (RELAX-AHF-2)).
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of mean terminal half-life about 7 to 8 hours after a 24-hour infusion (PMID 25511105). After about five half-lives almost none is left.
How long the doses were given: Phase 3: acute heart failure, 6,545 patients (RELAX-AHF-2): 48 hours, started within 16 hours of presentation; Phase 3: acute heart failure, 1,161 patients (RELAX-AHF): 48 hours; Phase 2: cirrhosis and portal hypertension, 40 patients: 2 hours, once.
When effects appear: unknown; no source on this page gives a time to effect for Serelaxin. Results reported in the studies are under Published Research.
Source: half-life: PMID 25511105; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Adverse events overall were similar to placebo in RELAX-AHF-2 (PMID 31433919); Low blood pressure and a fall in haemoglobin or haematocrit were more common than with usual care alone in RELAX-AHF-EU (PMID 30604559); Blood pressure fell by about 10 to 13 mmHg against placebo in the first hours of infusion in stable coronary disease (PMID 32065620); No antibodies to the drug developed after a 24-hour infusion in the liver-impairment study (PMID 25511105). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Serelaxin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Serelaxin was given only in hospital trials, mostly for 48 hours; the abstracts report adverse events at rates close to placebo, with these exceptions noted”).
Interactions
Unknown: a PubMed search for human interaction studies of Serelaxin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Serelaxin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Serelaxin's expected mass, 5,963.0 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (Never approved: Drugs@FDA (openFDA) returns no record (October 28, 2026), and the EMA's CHMP gave a negative opinion on Reasanz on January 23, 2014, confirmed on re-examination on May 22, 2014 (EMA medicine page, read October 28, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Serelaxin was given only in hospital trials, mostly for 48 hours; the abstracts report adverse events at rates close to placebo, with these exceptions noted.
Contraindications & Cautions
There is no label, so there are no formal contraindications. The trials set their own limits.
Legal Status
Serelaxin was developed by Novartis for acute heart failure and was never approved in the US or the EU.
Frequently Asked Questions
?What is serelaxin?
A recombinant copy of human relaxin-2, the hormone that relaxes blood vessels and raises kidney blood flow in pregnancy. It was tested as a 48-hour drip for people admitted with acute heart failure.
?Did serelaxin work?
Not on the outcomes that mattered. RELAX-AHF eased one breathlessness measure and showed fewer deaths at six months as a secondary result, but the 6,545-patient RELAX-AHF-2 trial found no difference in cardiovascular death or early worsening heart failure.
?Is serelaxin approved anywhere?
Not in the US or the EU. The European regulator refused it in 2014, there is no FDA record, and the maker later stopped supplying it to trials.
?What dose was used in the trials?
Nearly all heart-failure trials infused 30 µg per kilogram per day for 48 hours in hospital. That is a study amount, not a recommendation.
?How long does serelaxin last in the body?
Its mean terminal half-life was 7 to 8 hours after a 24-hour infusion; blood levels fall quickly once an infusion stops.
?Why did lab results improve while outcomes did not?
Serelaxin lowered markers of heart and kidney injury and improved kidney function early on, but an analysis of RELAX-AHF-2 found those changes did not lead to fewer deaths or readmissions.
References
- [clinical-trial] Metra M, et al. "Effects of Serelaxin in Patients with Acute Heart Failure." N Engl J Med, 2019;381(8):716-726. PMID: 31433919.
- [clinical-trial] Teerlink JR, et al. "Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial." Lancet, 2013;381(9860):29-39. PMID: 23141816.
- [clinical-trial] Felker GM, et al. "Effect of serelaxin on mode of death in acute heart failure: results from the RELAX-AHF study." J Am Coll Cardiol, 2014;64(15):1591-8. PMID: 25301463.
- [clinical-trial] Maggioni AP, et al. "Efficacy and safety of serelaxin when added to standard of care in patients with acute heart failure: results from a PROBE study, RELAX-AHF-EU." Eur J Heart Fail, 2019;21(3):322-333. PMID: 30604559.
- [clinical-trial] Voors AA, et al. "End-organ protective effect of serelaxin in patients hospitalized for heart failure: Results of the biomarker substudy of Relaxin in Acute Heart Failure-2 (RELAX-AHF-2)." Eur J Heart Fail, 2025;27(7):1215-1223. PMID: 39663924.
- [pubmed] Beldhuis IE, et al. "Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure." Clin Res Cardiol, 2023;112(7):901-910. PMID: 36656377.
- [clinical-trial] Ponikowski P, et al. "A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure." Eur Heart J, 2014;35(7):431-41. PMID: 24255129.
- [clinical-trial] Voors AA, et al. "Renal hemodynamic effects of serelaxin in patients with chronic heart failure: a randomized, placebo-controlled study." Circ Heart Fail, 2014;7(6):994-1002. PMID: 25286914.
- [clinical-trial] Corcoran D, et al. "Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial." Cardiovasc Res, 2021;117(1):320-329. PMID: 32065620.
- [clinical-trial] Sato N, et al. "Multicenter, Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Serelaxin in Japanese Patients With Acute Heart Failure." Circ J, 2015;79(6):1237-47. PMID: 25912697.
- [clinical-trial] Dahlke M, et al. "Safety and tolerability of serelaxin, a recombinant human relaxin-2 in development for the treatment of acute heart failure, in healthy Japanese volunteers and a comparison of pharmacokinetics and pharmacodynamics in healthy Japanese and Caucasian populations." J Clin Pharmacol, 2015;55(4):415-22. PMID: 25408331.
- [pubmed] Kobalava Z, et al. "Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study." Br J Clin Pharmacol, 2015;79(6):937-45. PMID: 25511105.
- [clinical-trial] Soubret A, et al. "Population pharmacokinetics of serelaxin in patients with acute or chronic heart failure, hepatic or renal impairment, or portal hypertension and in healthy subjects." Br J Clin Pharmacol, 2018;84(11):2572-2585. PMID: 30014598.
- [clinical-trial] Snowdon VK, et al. "Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial." PLoS Med, 2017;14(2):e1002248. PMID: 28245243.
- [clinical-trial] Gifford FJ, et al. "A phase 2 randomised controlled trial of serelaxin to lower portal pressure in cirrhosis (STOPP)." Trials, 2020;21(1):260. PMID: 32164767.
- [review] Teerlink JR, et al. "Effects of serelaxin in patients admitted for acute heart failure: a meta-analysis." Eur J Heart Fail, 2020;22(2):315-329. PMID: 31886953.
- [review] Yu L, et al. "Serelaxin, recombinant human relaxin-2, for heart failure patients: A systematic review and meta-analysis." Medicine (Baltimore), 2018;97(25):e11010. PMID: 29923986.
- [review] Sassoli C, et al. "Human Recombinant Relaxin (Serelaxin) as Anti-fibrotic Agent: Pharmacology, Limitations and Actual Perspectives." Curr Mol Med, 2022;22(3):196-208. PMID: 33687895.
- [other] PubChem CID 71300755, Serelaxin: formula C256H408N74O74S8, molecular weight 5963. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/71300755
- [other] European Medicines Agency, Reasanz (serelaxin): refused. CHMP negative opinion January 23, 2014, confirmed on re-examination May 22, 2014. Read October 28, 2026. https://www.ema.europa.eu/en/medicines/human/EPAR/reasanz
Sources & Citations
Every study on this page was read from its PubMed record on October 28, 2026. Regulatory status comes from Drugs@FDA (openFDA) and EMA's Reasanz page, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.