Open AccessInterleukin‐1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D‐ HART2 )
Author(s) -
Van Tassell Benjamin W.,
Buckley Leo F.,
Carbone Salvatore,
Trankle Cory R.,
Canada Justin M.,
Dixon Dave L.,
Abouzaki Nayef,
OddiErdle Claudia,
BiondiZoccai Giuseppe,
Arena Ross,
Abbate Antonio
Publication year - 2017
Publication title -
clinical cardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.263
H-Index - 72
eISSN - 1932-8737
pISSN - 0160-9289
DOI - 10.1002/clc.22719
Subject(s) - medicine , anakinra , heart failure , ejection fraction , heart failure with preserved ejection fraction , cardiology , placebo , clinical trial , clinical endpoint , cardiorespiratory fitness , disease , pathology , alternative medicine
Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of confirmed HF cases in the United States. However, there are no highly effective evidence-based treatments currently available for these patients. Inflammation correlates positively with adverse outcomes in HF patients. Interleukin (IL)-1, a prototypical inflammatory cytokine, has been implicated as a driver of diastolic dysfunction in preclinical animal models and a pilot clinical trial. The Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2) is a phase 2, 2:1 randomized, double-blind, placebo-controlled clinical trial that will test the hypothesis that IL-1 blockade with anakinra (recombinant human IL-1 receptor antagonist) improves (1) cardiorespiratory fitness, (2) objective evidence of diastolic dysfunction, and (3) elevated inflammation in patients with HFpEF (http://www.ClinicalTrials.gov NCT02173548). The co-primary endpoints will be placebo-corrected interval changes in peak oxygen consumption and ventilatory efficiency at week 12. In addition, secondary and exploratory analyses will investigate the effects of IL-1 blockade on cardiac structure and function, systemic inflammation, endothelial function, quality of life, body composition, nutritional status, and clinical outcomes. The D-HART2 clinical trial will add to the growing body of evidence on the role of inflammation in cardiovascular disease, specifically focusing on patients with HFpEF.