Evidence map›Paper›PMID 39829393›Full record

ArticleESC heart failure2025

Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re-PHIRE.

Marcin Ufnal, Kathleen Connolly, Marcus Millegard, Elena Surkova, Marco Guazzi, Diana Bonderman, Justin Ezekowitz, Finn Gustafsson, Michał Ciurzyński, Raquel López Vilella and 8 more

Abstract readClinical Trial Protocol
In one paragraph

Article in ESC heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Marcin UfnalEarly Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland.
Kathleen ConnollyEarly Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Marcus MillegardEarly Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Elena SurkovaEarly Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Marco GuazziUniversity of Milan School of Medicine, San Paolo University Hospital, Milan, Italy.
Diana BondermanDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
Justin EzekowitzCanadian VIGOUR Centre, University of Alberta, Edmonton, Canada.
Finn GustafssonThe Heart Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Michał CiurzyńskiDepartment of Internal Medicine and Cardiology with the Centre for Management of Venous Thromboembolic Disease, Medical University of Warsaw, Warsaw, Poland.
Raquel López VilellaHeart Failure and Transplantation Unit, La Fe University and Polytechnic Hospital, Valencia, Spain.
Tariq AhmadHeart Failure Program, Yale School of Medicine, New Haven, Connecticut, USA.
Roy GardnerScottish National Advanced Heart Failure Service, Golden Jubilee National Hospital, Clydebank, UK.
Pavel Jansa2nd Department of Medicine, Charles University and General University Hospital, Prague, Czechia.
Sandra van WijkDepartment of Cardiology, Zuyderland Medical Center, Heerlen, The Netherlands.
Koichiro KinugawaSecond Department of Internal Medicine, University of Toyama, Toyama, Japan.
Erik BjörklundDepartment of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Zhi-Cheng JingDepartment of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
Stephan RosenkranzDepartment of Cardiology, Pulmonology, and Intensive Care Medicine, Center for Molecular Medicine Cologne (CMMC), Cologne Cardiovascular Research Center (CCRC), Medical Faculty, University of Cologne, Cologne, Germany.

Funding

AstraZeneca
6 · The paper itself

Abstract

aimsDespite receiving guideline-directed medical heart failure (HF) therapy, patients with pulmonary hypertension associated with left heart disease (PH-LHD) experience higher mortality and hospitalization rates than the general HF population. AZD3427 is a functionally selective, long-acting mimetic of relaxin, a hormone that has the potential to induce vasodilation and prevent fibrosis. In a phase 1b study conducted in patients with HF, AZD3427 demonstrated a favourable safety and pharmacokinetic profile. To address the unmet medical need in patients with PH-LHD in the context of HF, AZD3427 is currently under development as a potential treatment option. METHODS AND

resultsThe Re-PHIRE study is a phase 2b, randomized, double-blind, placebo-controlled, multicentre, dose-ranging study to evaluate the effect of AZD3427 on a broad range of PH-LHD phenotypes. In total, 220 patients will be randomized to four treatment groups to receive a subcutaneous injection of AZD3427 or placebo every 2 weeks for 24 weeks. The primary endpoint of the study is the change in pulmonary vascular resistance in patients treated with AZD3427 versus placebo after 24 weeks of treatment. Key secondary endpoints include changes in mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, 6-min walking distance, N-terminal pro B-type natriuretic peptide levels, echocardiographic parameters, and health-related quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire).

conclusionsRe-PHIRE is the first study of a relaxin mimetic in patients with PH-LHD. The insights gained from the Re-PHIRE study are expected to inform the further development of AZD3427 in the PH-LHD population, including identifying the most suitable pulmonary hypertension and HF phenotypes for treatment.

Indexed as

Heart FailureHypertension, PulmonaryRelaxinAgedClinical Trials, Phase II as TopicDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMaleMiddle AgedMulticenter Studies as TopicRandomized Controlled Trials as TopicVascular ResistanceRelaxinHeart failureLeft heart diseasePulmonary hypertensionPulmonary vascular resistanceRelaxin

Identifiers

PMID39829393
PMCPMC12055356

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.