Home › Trials › NCT03514108

Testing hydralazine and metformin for heart failure patients

A Randomized, Double-blind, Placebo Controlled Study (DANHEART): Hydralazine-ISDN in Patients With Chronic Heart Failure - Hydralazine Heart Failure Trial (H-HeFT) and Metformin in Patients With Chronic Heart Failure and Diabetes or Insulin Resistance - Metformin Heart Failure Trial (Met-HeFT)

Phase 4 Interventional Aarhus University Hospital · NCT03514108

This study is testing if combining hydralazine with isosorbide dinitrate and metformin can help people with chronic heart failure, especially those with type 2 diabetes, feel better and stay out of the hospital.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment1500 (estimated)
Ages18 Years and up
SexAll
SponsorAarhus University Hospital Academic / other
Locations26 sites (Holbæk, Region Sjælland and 25 other locations)
Trial IDNCT03514108 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of two drug combinations in patients with chronic heart failure: hydralazine combined with isosorbide dinitrate, and metformin for those with type 2 diabetes or insulin resistance. It is a double-blind, placebo-controlled trial aimed at reducing mortality and hospitalizations due to worsening heart failure. The study also explores secondary outcomes such as the reduction of new-onset diabetes in heart failure patients. Participants must have a reduced left ventricular ejection fraction (LVEF) and meet specific heart failure criteria.

Who should consider this trial

Good fit: Ideal candidates are patients with chronic heart failure, NYHA-class II, III, or IV, and reduced LVEF of 40% or less.

Not a fit: Patients with heart failure who do not have reduced LVEF or those who are not classified as NYHA-class II, III, or IV may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce mortality and hospitalizations in heart failure patients, particularly those with diabetes or insulin resistance.

How similar studies have performed: Other studies have shown promise in using similar drug combinations for heart failure, but this specific approach is being tested for the first time.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

General inclusion criteria for both H-HeFT and Met-HeFT

* Patients with chronic heart failure
* NYHA-class II, III or IV
* LVEF \</= 40% within 12 months prior to screening. The echocardiography should (i) be performed after uptitration in heart failure medication and (ii) LVEF from the most recently performed echocardiographic study should be used and (iii) LVEF must not be measured during rapid atrial fibrillation, i.e. heart rate \>110/min) and (iiii) the echocardiography should be performed at least 3 months after CRT-implantation.
* Patients should be uptitrated to recommended or maximally tolerated dose of ACE-I/ARB/ARNI (unless contraindicated) and beta-blocker (unless contraindicated). If indicated, an aldosterone receptor antagonist should be given (unless contraindicated).
* A CRT device should be implanted, if indicated and accepted by the patient and patients with a CRT device should be treated for \> 3 months.
* Implantation of an ICD unit should be planned or already done, if indicated and accepted by the patient. The patient can be included in the study before a planned ICD implantation has been performed.
* Informed consent

Specific inclusion criteria for only H-HeFT:

* Systolic blood pressure ≥100 mmHg
* NT-proBNP \> 350 pg/ml or BNP \> 80 pg/ml (in patients treated with ARNI, NT-proBNP must be used)

Specific inclusion criteria for only Met-HeFT:

Patients must have a diagnosis of type 2 diabetes or insulin resistance or diabetes risk. This includes 1 or more of any of the following:

* A previous diagnosis of type 2 diabetes at any time without Metformin treatment during the last 3 months
* HbA1c ≥ 5.5 % (≥ 37 mmol/mol) within 12 months prior to screening
* Fasting P-glucose ≥ 5.6 mmol/l within 12 months prior to screening (measured when the patient in stable condition / has no intercurrent illness)
* Body mass index ≥ 30 kg/m2
* If oral glucose tolerance testing (OGTT) has been performed at any time prior to randomization: 2 hour P-glucose ≥ 7.8 mmol/l
* In addition, patients in Met-HeFT must have eGFR ≥ 35 ml/min (MDRD)

Patients are randomized through an internet based randomization module. Patients can be allocated to a) both H-HeFT and Met-HeFT or to b) only H-HeFT or to c) only Met-HeFT.

Where this trial is running

Holbæk, Region Sjælland and 25 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Heart FailureDiabetesHeart failureInsulin resistanceMetforminHydralazineIsosorbide Dinitrate
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.