Re-PERFUSE: Phase 1b study of AZD3427, a novel relaxin receptor agonist, on renal perfusion in HFrEF patients.

IF 3.7 2区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Marcin Ufnal, Macarena P Quintana-Hayashi, Kathleen Connolly, Daniel Pettersen, Zsolt Cselényi, Aurelija Jucaite, Magnus Schou, Andrea Varrone, Melanie Chan, Lars H Lund
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引用次数: 0

Abstract

Aims: Renal impairment frequently coexists with heart failure (HF) and is associated with increased risk of poor clinical outcomes. This highlights the urgent need for therapies targeting both cardiac and renal dysfunction. AZD3427, a long-acting recombinant fusion protein and relaxin analogue that selectively activates the relaxin family peptide receptor 1 (RXFP1), showed trends of increased stroke volume and estimated glomerular filtration rate (eGFR) in HF patients (NCT04630067). The hypothesis is that AZD3427 may enhance GFR by expanding the functional renal cortex volume and improving renal perfusion.

Methods and results: The Re-PERFUSE study (NCT06611423) is a Phase 1b, randomised, double-blind, placebo-controlled trial aimed at evaluating the effects of AZD3427 on renal perfusion in patients with HF and reduced ejection fraction (HFrEF) with reduced eGFR. Patients with HF, EF ≤ 40% and an eGFR of 30 to 90 mL/min/1.73 m2, assessed by the CKD-EPI 2021, will receive a single dose of subcutaneous AZD3427 (n = 6) or placebo (n = 6). Intravenous dopamine will serve as a positive control for increased renal blood flow. Positron emission tomography (PET) imaging with [15O]-labelled water will be used to measure renal cortex blood flow pre- and post-treatment, allowing differentiation between global and focal renal blood flow changes and providing insights into potential nephron recruitment and increased filtration membrane area. Safety and tolerability will be assessed through monitoring of adverse events, clinical laboratory tests and vital signs.

Conclusions: This study, alongside other ongoing AZD3427 studies, aims to evaluate the dual effects of AZD3427 in improving both cardiac and renal function. These insights could guide the development of future therapeutic strategies for managing HF and renal impairment.

Re-PERFUSE:新型松弛素受体激动剂AZD3427对HFrEF患者肾灌注的1b期研究。
目的:肾功能损害经常与心力衰竭(HF)共存,并与临床预后不良的风险增加相关。这突出了针对心脏和肾脏功能障碍的治疗的迫切需要。AZD3427是一种长效重组融合蛋白和松弛素类似物,可选择性激活松弛素家族肽受体1 (RXFP1),在HF患者中显示出卒中容量和肾小球滤过率(eGFR)增加的趋势(NCT04630067)。假设AZD3427可能通过扩大功能性肾皮质体积和改善肾灌注来提高GFR。方法和结果:Re-PERFUSE研究(NCT06611423)是一项1b期、随机、双盲、安慰剂对照试验,旨在评估AZD3427对HF和射血分数降低(HFrEF)伴eGFR降低患者肾灌注的影响。CKD-EPI 2021评估的HF, EF≤40%,eGFR为30至90 mL/min/1.73 m2的患者将接受单剂量皮下AZD3427 (n = 6)或安慰剂(n = 6)。静脉注射多巴胺可作为肾血流量增加的阳性对照。[15O]标记水的正电子发射断层扫描(PET)成像将用于测量治疗前后的肾皮质血流量,从而区分整体和局灶性肾血流量变化,并提供潜在的肾元募集和过滤膜面积增加的信息。将通过监测不良事件、临床实验室检查和生命体征来评估安全性和耐受性。结论:该研究与其他正在进行的AZD3427研究一起,旨在评估AZD3427在改善心脏和肾脏功能方面的双重作用。这些见解可以指导未来心衰和肾损害治疗策略的发展。
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来源期刊
ESC Heart Failure
ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine
CiteScore
7.00
自引率
7.90%
发文量
461
审稿时长
12 weeks
期刊介绍: ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.
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