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Clinical Trial
. 2022 Jun 15;20(1):270.
doi: 10.1186/s12967-022-03466-9.

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study

Benjamin Van Tassell  1   2 , Virginia Mihalick  3 , Georgia Thomas  3 , Amr Marawan  3 , Azita H Talasaz  4 , Juan Lu  5 , Le Kang  6 , Amy Ladd  3 , Juan Ignacio Damonte  3 , Dave L Dixon  3   4 , Roshanak Markley  3 , Jeremy Turlington  3 , Emily Federmann  3 , Marco Giuseppe Del Buono  3 , Giuseppe Biondi-Zoccai  7   8 , Justin M Canada  3 , Ross Arena  9 , Antonio Abbate  3
Affiliations
Clinical Trial

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study

Benjamin Van Tassell et al. J Transl Med. .

Abstract

Background: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF.

Method: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes.

Discussion: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF.

Trial registration: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.

Keywords: Anakinra; HFrEF; Heart failure; IL-1; Interleukin-1; Target therapy; Treatment.

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Conflict of interest statement

Dr. Abbate (AA) has served as consultant to Swedish Orphan Biovitrum in the past. Dr. Van Tassell (BVT) has served as consultant to Swedish Orphan Biovitrum in the past. No other authors have relevant disclosures.

Figures

Fig. 1
Fig. 1
Schematic protocol of the REDHART2 study. Schematic protocol of the REDHART2 study to investigate the potential effects of anakinra in a randomized double-blind placebo-controlled clinical trial. Patients will be followed for 24 weeks. Lab tests, questionnaires, bio-electrical impedance analysis, echocardiogram and cardiopulmonary exercise testing will be done at baseline, 6, 12, and 24 weeks. Visit 1.5 (after 2 weeks) is considered a safety follow-up assessment
See this image and copyright information in PMC

References

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