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)
Overview
- Phase
- Phase 4
- Intervention
- Metformin Hydrochloride
- Conditions
- Heart Failure
- Sponsor
- Henrik Wiggers
- Enrollment
- 1100
- Locations
- 50
- Primary Endpoint
- H-HeFT combined primary endpoint
- Status
- Completed
- Last Updated
- 25 days ago
Overview
Brief 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.
- The first hypothesis is that hydralazine in combination with isosorbide dinitrate can reduce mortality and hospitalization with worsening heart failure in chronic heart failure patients with reduced LVEF.
- The second hypothesis is that treatment with metformin in chronic heart failure patients with reduced LVEF and type 2 diabetes / diabetes risk / insulin resistance 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.
Investigators
Henrik Wiggers
Professor, Consultant, MD, PhD, DMSc
Aarhus University Hospital
Eligibility 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
Exclusion Criteria
- Not provided
Arms & Interventions
Metformin
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.
Intervention: Metformin Hydrochloride
Placebo (Metformin)
Tablet Placebo 500 mg 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily). Average treatment period 4 years.
Intervention: Placebo Oral Tablet
Placebo (Hydralazine Isosorbide Dinitrate)
Tablet Placebo 2 tablets x 3 daily. Average treatment period 4 years.
Intervention: Placebo Oral Tablet
Hydralazine Isosorbide Dinitrate
Tablet BiDil (Hydralazine 37.5 mg/ isosorbide dinitrate (ISDN) 20 mg) 2 tablets x 3 daily. Average treatment period 4 years.
Intervention: Hydralazine Isosorbide Dinitrate
Outcomes
Primary Outcomes
H-HeFT combined primary endpoint
Time Frame: Through study completion, an average of 4 years
Combined endpoint: Death or hospitalization with worsening heart failure or an urgent visit resulting in intravenous therapy or metolazone therapy for heart failure or heart transplantation or implantation of a LVAD.
Met-HeFT combined primary endpoint
Time Frame: Through study completion, an average of 4 years
Combined endpoint: Death or hospitalization with worsening heart failure or an urgent visit resulting in intravenous therapy or metolazone therapy for heart failure or heart transplantation or implantation of a LVAD or acute myocardial infarction or stroke
Secondary Outcomes
- H-HeFT Death(Through study completion, an average of 4 years)
- H-HeFT: Heart failure events(Through study completion, an average of 4 years)
- H-HeFT: Death or cardiovascular hospitalization(Through study completion, an average of 4 years)
- H-HeFT combined primary endpoint of total (first and recurrent) events(Through study completion, an average of 4 years)
- H-HeFT: All-cause, total (first and subsequent) hospitalizations(Through study completion, an average of 4 years)
- H-HeFT: Change in NT-proBNP from baseline to final follow-up(Through study completion, an average of 4 years)
- H-HeFT: Cardiovascular hospitalizations(Through study completion, an average of 4 years)
- Met-HeFT combined endpoint of total (first and recurrent) events in the primary endpoint(Through study completion, an average of 4 years)
- Met-HeFT secondary endpoint: Death(Through study completion, an average of 4 years)
- Met-HeFT: Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure or heart transplantation or implantation of a LVAD(Through study completion, an average of 4 years)
- Met-HeFT Extended clinical endpoint (first event analysis): The primary endpoint or coronary revascularization or non-coronary revascularization or limb amputation.(Through study completion, an average of 4 years)
- Met-HeFT secondary endpoint: Acute myocardial infarction(Through study completion, an average of 4 years)
- Met-HeFT secondary endpoint: Stroke(Through study completion, an average of 4 years)
- Met-HeFT secondary endpoint: New onset type 2 diabetes(Through study completion, an average of 4 years)
- Met-HeFT secondary endpoint: Hospitalization or death caused by lactic acidosis.(Through study completion, an average of 4 years)
- Met-HeFT: All-cause, total (first and subsequent) hospitalizations(Through study completion, an average of 4 years)
- Met-HeFT: Change in NT-proBNP from baseline to final follow-up(Through study completion, an average of 4 years)
- Met-HeFT: Cardiovascular hospitalizations(Through study completion, an average of 4 years)