DANHEART (H-HeFT and Met-HeFT)

Heart Failure Clinical Trial

— DANHEART  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03514108
• Other study ID #: DANHEART
• Secondary ID: 2015-002150-12
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2018
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2023
• Source: Aarhus University Hospital
• Contact: Henrik Wiggers, MD, PhD
• Phone: +45 40136627
• Email: henrikwiggers[@]dadlnet.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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. 1. The first hypothesis is that hydralazine in combination with isosorbide dinitrate can reduce mortality and hospitalization with worsening heart failure. 2. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Heart Failure

Intervention

Drug:
• Hydralazine Isosorbide Dinitrate
Tablet BiDil (Hydralazine 37.5 mg/ Isosorbide Dinitrate (ISDN) 20 mg) 2 tablets x 3 daily
• Placebo Oral Tablet
2 tablets x 3 daily
• Metformin Hydrochloride
Tablet Metformin hydrochloride 500 mg 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily)
• Placebo Oral Tablet
2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily)

Locations

Country	Name	City	State
Denmark	Sygehus Sønderjylland, Aabenraa	Aabenraa
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Amager Hospital	Copenhagen
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Gentofte Hospital	Copenhagen
Denmark	Glostrup Hospital	Copenhagen
Denmark	Herlev Hospital	Copenhagen
Denmark	Hvidovre Hospital	Copenhagen
Denmark	Rigshospitalet	Copenhagen
Denmark	Sydvestjysk Sygehus, Esbjerg	Esbjerg
Denmark	Herning Hospital	Herning
Denmark	Nordsjællands Hospital Hillerød	Hillerød
Denmark	Regionshospital Nordjylland, Hjørring	Hjørring
Denmark	Holbæk Hospital	Holbæk
Denmark	Horsens Hospital	Horsens
Denmark	Kolding Hospital	Kolding
Denmark	Nykøbing Falster Hospital	Nykøbing Falster
Denmark	Odense University Hospital	Odense
Denmark	Randers Hospital	Randers
Denmark	Sjællands Universitetshospital, Roskilde	Roskilde
Denmark	Silkeborg Hospital	Silkeborg
Denmark	Slagelse Sygehus	Slagelse
Denmark	Vejle Hospital	Vejle
Denmark	Viborg Hospital	Viborg

Sponsors (6)

Lead Sponsor	Collaborator
Henrik Wiggers	Danish Council for Independent Research, Danish Heart Foundation, The Aase og Ejnar Danielsen Foundation, The Danish Regions: Foundation for Medical Research, The Novo Nordisk Foundation

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	H-HeFT combined endpoint: Death or hospitalization with worsening heart failure or urgent heart failure visit	Death or hospitalization with worsening heart failure or urgent heart failure visit resulting in intravenous therapy or metolazone treatment for heart failure.	Through study completion, an average of 4 years
Primary	Met-HeFT combined endpoint: Death or hospitalization with worsening heart failure or acute myocardial infarction or stroke or urgent heart failure visit	Death or hospitalization with worsening heart failure or acute myocardial infarction or stroke or urgent visit resulting in intravenous therapy or metolazone treatment for heart failure	Through study completion, an average of 4 years
Secondary	H-HeFT secondary endpoint: Death	Death	Through study completion, an average of 4 years
Secondary	H-HeFT secondary endpoint: Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure	Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure	Through study completion, an average of 4 years
Secondary	H-HeFT secondary endpoint: Combined endpoint: Death or cardiovascular hospitalization or urgent heart failure visit	Combined endpoint: Death or cardiovascular hospitalizations (hospitalization with worsening heart failure, acute myocardial infarction, or stroke) or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure	Through study completion, an average of 4 years
Secondary	Met-HeFT secondary endpoint: Extended clinical endpoint: The primary endpoint or coronary revascularization or non-coronary revascularization or limb amputation.	Extended clinical endpoint: The primary endpoint or coronary revascularization or non-coronary revascularization or limb amputation.	Through study completion, an average of 4 years
Secondary	Met-HeFT secondary endpoint: Death	Death	Through study completion, an average of 4 years
Secondary	Met-HeFT secondary endpoint: Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure	Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure	Through study completion, an average of 4 years
Secondary	Met-HeFT secondary endpoint: Acute myocardial infarction	Acute myocardial infarction	Through study completion, an average of 4 years
Secondary	Met-HeFT secondary endpoint: Stroke	Stroke	Through study completion, an average of 4 years
Secondary	Met-HeFT secondary endpoint: New onset type 2 diabetes	New onset type 2 diabetes	Through study completion, an average of 4 years
Secondary	Met-HeFT secondary endpoint: Hospitalization or death caused by lactate acidosis.	Hospitalization or death caused by lactate acidosis.	Through study completion, an average of 4 years