Pragmatic Design of Randomized Clinical Trials for Heart Failure: Rationale and Design of the TRANSFORM-HF Trial

TRANSFORM-HF Investigators

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Randomized clinical trials are the foundation of evidence-based medicine and central to practice guidelines and patient care decisions. Nonetheless, randomized trials in heart failure (HF) populations have become increasingly difficult to conduct and are frequently associated with slow patient enrollment, highly selected populations, extensive data collection, and high costs. The traditional model for HF trials has become particularly difficult to execute in the United States, where challenges to site-based research have frequently led to modest U.S. representation in global trials. In this context, the TRANSFORM-HF (Torsemide Comparison with Furosemide for Management of Heart Failure) trial aims to overcome traditional trial challenges and compare the effects of torsemide versus furosemide among patients with HF in the United States. Loop diuretic agents are regularly used by most patients with HF and practice guidelines recommend optimal use of diuretic agents as key to a successful treatment strategy. Long-time clinical experience has contributed to dominant use of furosemide for loop diuretic therapy, although preclinical and small clinical studies suggest potential advantages of torsemide. However, due to the lack of appropriately powered clinical outcome studies, there is insufficient evidence to conclude that torsemide should be routinely recommended over furosemide. Given this gap in knowledge and the fundamental role of loop diuretic agents in HF care, the TRANSFORM-HF trial was designed as a prospective, randomized, event-driven, pragmatic, comparative-effectiveness study to definitively compare the effect of a treatment strategy of torsemide versus furosemide on long-term mortality, hospitalization, and patient-reported outcomes among patients with HF. (TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure [TRANSFORM-HF]; NCT03296813)

Original languageEnglish (US)
Pages (from-to)325-335
Number of pages11
JournalJACC: Heart Failure
Volume9
Issue number5
DOIs
StatePublished - May 1 2021

Bibliographical note

Funding Information:
TRANSFORM-HF is supported through cooperative agreements from the National Heart, Lung, and Blood Institute: U01-HL125478 and U01-HL125511. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Dr. Greene has received research support from the American Heart Association, Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; has served on advisory boards for Amgen and Cytokinetics; and has served as a consultant for Amgen and Merck. Dr. Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, and Windtree Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 American College of Cardiology Foundation

Keywords

  • clinical trial
  • diuretic
  • furosemide
  • heart failure
  • pragmatic
  • torsemide

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Review

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