Trial | NCT03514108  Report issue

Title

DANHEART (H-HeFT and Met-HeFT)
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

    Phase 4

  • Study Type

    Interventional

  • Status

    Recruiting

  • Study Participants

    1500
The present study is testing in a combined design to types of drugs in patients with chronic heart failure: 1) Hydralazine in combination with isosorbide dinitrate (BiDil) and 2) Metformin hydrochloride. The study is double blind, placebo controlled.

The first hypothesis is that hydralazine in combination with isosorbide dinitrate can reduce mortality and hospitalization with worsening heart failure.
The second hypothesis is that treatment of underlying insulin resistance/ type 2 diabetes with metformin in heart failure patients with moderately to severely reduced LVEF can reduce mortality and cardiovascular hospitalizations. Among secondary endpoints are reduction in new-onset diabetes in heart failure patients with insulin resistance and diabetes risk profile and patient safety.
Study Started
Mar 01
2018
Primary Completion
Dec 31
2026
Anticipated
Study Completion
Dec 31
2026
Anticipated
Last Update
May 31
2023

Drug Placebo Oral Tablet

2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily)

Drug Hydralazine Isosorbide Dinitrate

Tablet BiDil (Hydralazine 37.5 mg/ Isosorbide Dinitrate (ISDN) 20 mg) 2 tablets x 3 daily

  • Other names: BiDil

Drug Placebo Oral Tablet

2 tablets x 3 daily

Drug Metformin Hydrochloride

Tablet Metformin hydrochloride 500 mg 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily)

Hydralazine Isosorbide Dinitrate Active Comparator

Tablet BiDil (Hydralazine 37.5 mg/ isosorbide dinitrate (ISDN) 20 mg) 2 tablets x 3 daily. Average treatment period 4 years.

Placebo (Hydralazine Isosorbide Dinitrate) Placebo Comparator

Tablet Placebo 2 tablets x 3 daily. Average treatment period 4 years.

Metformin Active Comparator

Tablet Metformin hydrochloride 500 mg 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily). Average treatment period 4 years.

Placebo (Metformin) Placebo Comparator

Tablet Placebo 500 mg 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily). Average treatment period 4 years.

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.
No Results Posted