ArticleEuropean journal of heart failure2023
Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction.
Article in European journal of heart failure, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Immunology of heart failure with preserved ejection fraction.Expert review of clinical immunology · 2025Pooled it
- Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial.Nature medicine · 2026Trial
- The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of mitiperstat.British journal of clinical pharmacology · 2024Trial
- Pharmacokinetics and Tolerability of the Novel Myeloperoxidase Inhibitor Mitiperstat in Healthy Japanese and Chinese Volunteers.Clinical drug investigation · 2024Trial
- The myeloperoxidase inhibitor mitiperstat (AZD4831) does not prolong the QT interval at expected therapeutic doses.Pharmacology research & perspectives · 2024Trial
- Review
- Population Pharmacokinetics of the Novel Myeloperoxidase Inhibitor Mitiperstat.Pharmacology research & perspectives · 2026Article
- Novel biomarkers distinguish heart failure with preserved vs reduced ejection fraction.ESC heart failure · 2026Observational
- Targeting neutrophil extracellular traps (NETs): a promising immunotherapeutic approach for pulmonary diseases.Molecular biology reports · 2026Review
- The Potential Connection Between Mechanical Stress and Heart Failure with Preserved Ejection Fraction: Mechanistic Insights and Therapeutic Potential.International journal of medical sciences · 2026Review
- Heart Failure in the Modern Era: A Narrative Overview of Recent Research from 2022-2025.Journal of cardiovascular development and disease · 2025Review
- Inflammatory Biomarkers in Heart Failure: Clinical Perspectives on hsCRP, IL-6 and Emerging Candidates.Current heart failure reports · 2025Review
- Heart failure with preserved ejection fraction in cancer patients and survivors. A scientific statement of the Heart Failure Association of the ESC and the ESC Council of Cardio-Oncology.European journal of heart failure · 2025Article
- Immunometabolism in heart failure.Nature reviews. Cardiology · 2025Review
- Immuno-haemostatic dysregulation in heart failure with preserved ejection fraction.ESC heart failure · 2025Article
- Myeloperoxidase inhibition in the landscape of anti-inflammatory therapies for heart failure with preserved ejection fraction: the ENDEAVOR trial.Heart failure reviews · 2025Review
- The Hidden Price of Plenty: Oxidative Stress and Calorie-Induced Cardiometabolic Dysfunction.Life (Basel, Switzerland) · 2025Review
- Multifaceted roles of neutrophils in cardiac disease.Journal of leukocyte biology · 2025Review
- In Situ Metal-Organic Framework Growth in Serum Encapsulates and Depletes Abundant Proteins for Integrated Plasma Proteomics.ACS nano · 2025Article
- Targeting vascular adhesion protein-1 and myeloperoxidase with a dual inhibitor SNT-8370 in preclinical models of inflammatory disease.Nature communications · 2025Article
Corrections and comments
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Authors and funding
19 authors at 15 institutions in 14 countries.
Funding
Abstract
aimsMitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF.
methodsIn phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo.
conclusionENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.
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Registered trials
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 OpenQuestion graph.