The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT)

Henrik Wiggers, Lars Køber, Gunnar Gislason, Morten Schou, Mikael Kjær Poulsen, Søren Vraa, Olav Wendelbo Nielsen, Niels Eske Bruun, Helene Nørrelund, Malene Hollingdal, Anders Barasa, Morten Bøttcher, Karen Dodt, Vibeke Brogaard Hansen, Gitte Nielsen, Anne Sejr Knudsen, Jens Lomholdt, Kirsten Vilain Mikkelsen, Bartlomiej Jonczy, Jens Brønnum-Schou, Monica Petronela Poenaru, Jawdat Abdulla, Ilan Raymond, Kiomars Mahboubi, Karen Sillesen, Kristine Serup-Hansen, Jette Sandberg Madsen, Søren Lund Kristensen, Anders Hostrup Larsen, Hans Erik Bøtker, Christian Torp-Petersen, Hans Eiskjær, Jacob Møller, Christian Hassager, Flemming Hald Steffensen, Bo Martin Bibby, Jens Refsgaard, Dan Eik Høfsten, Søren Mellemkjær, Finn Gustafsson, Henrik Wiggers, Lars Køber, Gunnar Gislason, Morten Schou, Mikael Kjær Poulsen, Søren Vraa, Olav Wendelbo Nielsen, Niels Eske Bruun, Helene Nørrelund, Malene Hollingdal, Anders Barasa, Morten Bøttcher, Karen Dodt, Vibeke Brogaard Hansen, Gitte Nielsen, Anne Sejr Knudsen, Jens Lomholdt, Kirsten Vilain Mikkelsen, Bartlomiej Jonczy, Jens Brønnum-Schou, Monica Petronela Poenaru, Jawdat Abdulla, Ilan Raymond, Kiomars Mahboubi, Karen Sillesen, Kristine Serup-Hansen, Jette Sandberg Madsen, Søren Lund Kristensen, Anders Hostrup Larsen, Hans Erik Bøtker, Christian Torp-Petersen, Hans Eiskjær, Jacob Møller, Christian Hassager, Flemming Hald Steffensen, Bo Martin Bibby, Jens Refsgaard, Dan Eik Høfsten, Søren Mellemkjær, Finn Gustafsson

Abstract

Objectives: The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT).

Methods: Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years.

Results: As of May 2020, 296 patients have been randomized at 20 centers in Denmark.

Conclusion: The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Trial registration: ClinicalTrials.gov NCT03514108.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Overall study design and endpoints in the DANHEART study (including the 2 substudies H-HeFT and Met-HeFT).
Figure 2
Figure 2
Study drug dosing, adjustment and control.

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