Trial reportNature medicine2026
Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial.
Trial report in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04986202 (A Randomised, Double-blind, Placebo-controlled, Multi-center Sequential Phase 2b and Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 Administered for Up to 48 Weeks in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%), which is not on this map. Not yet cited in PubMed.
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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.
A Randomised, Double-blind, Placebo-controlled, Multi-center Sequential Phase 2b and Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 Administered for Up to 48 Weeks in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%
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Authors and funding
27 authors.
Funding
Abstract
Myeloperoxidase (MPO)-derived oxidants reduce nitric oxide bioavailability and promote coronary microvascular dysfunction, cardiomyocyte stiffening and interstitial fibrosis-mechanisms implicated in the pathogenesis of heart failure with preserved and mildly reduced ejection fraction. Here, in a multicenter, randomized, double-blind, placebo-controlled, three-arm, parallel-group phase 2b trial of patients with heart failure and an ejection fraction of >40%, we evaluated whether treatment with the MPO inhibitor mitiperstat versus placebo for 48 weeks improved symptoms and exercise function at 16 weeks (the co-primary endpoints were the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and 6-minute walk distance (6MWD)). Secondary endpoints included changes in natriuretic peptides and inflammatory markers (up to 48 weeks) and echocardiographic parameters (up to 24 weeks). In total, 711 patients (45% women) were randomized 1:1:1 to mitiperstat 2.5 mg, mitiperstat 5 mg or placebo. Mitiperstat (pooled doses) did not improve KCCQ-TSS (placebo-corrected difference in mean change from baseline, -1.4 points (95% confidence interval (CI) -3.9, 1.2; P = 0.29), 6MWD (3.8 m (95% CI -3.1, 10.8)); P = 0.28) or any secondary endpoint. Adverse and serious adverse events, including infections, were similar among groups except for maculopapular rash (mitiperstat, 3.6%; placebo, 0.4%). These results indicate that mitiperstat was safe and well tolerated but did not improve symptoms or exercise function in chronic heart failure with preserved or mildly reduced ejection fraction. ClinicalTrials.gov registration: NCT04986202 .
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