DANHEART (H-HeFT and Met-HeFT)
- Conditions
- Heart FailureDiabetes
- Interventions
- Registration Number
- NCT03514108
- Lead Sponsor
- Henrik Wiggers
- 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.
1. 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.
2. 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1500
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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Hydralazine Isosorbide Dinitrate Hydralazine Isosorbide Dinitrate Tablet BiDil (Hydralazine 37.5 mg/ isosorbide dinitrate (ISDN) 20 mg) 2 tablets x 3 daily. Average treatment period 4 years. Placebo (Metformin) Placebo Oral Tablet Tablet Placebo 500 mg 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily). Average treatment period 4 years. Metformin Metformin Hydrochloride 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 (Hydralazine Isosorbide Dinitrate) Placebo Oral Tablet Tablet Placebo 2 tablets x 3 daily. Average treatment period 4 years.
- Primary Outcome Measures
Name Time Method H-HeFT combined primary endpoint 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 of total (first and recurrent) events Through study completion, an average of 4 years Combined endpoint of total (first and recurrent) events: 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 Outcome Measures
Name Time Method H-HeFT: Recurrent event analysis Through study completion, an average of 4 years Total (first and recurrent) events: 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.
H-HeFT: Change in NT-proBNP from baseline to final follow-up Through study completion, an average of 4 years Change in NT-proBNP
H-HeFT secondary endpoint: Combined endpoint: Death or cardiovascular hospitalization or urgent heart failure visit Through study completion, an average of 4 years 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
H-HeFT secondary endpoint: Death Through study completion, an average of 4 years Death
H-HeFT secondary endpoint: 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 Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure
H-HeFT: All-cause, total (first and subsequent) hospitalizations Through study completion, an average of 4 years Any hospitalization
Met-HeFT secondary endpoint: Combined endpoint of first event Through study completion, an average of 4 years Combined endpoint of first event: 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
Met-HeFT secondary endpoint: Extended clinical endpoint (recurrent events): The primary endpoint or coronary revascularization or non-coronary revascularization or limb amputation. Through study completion, an average of 4 years Extended clinical endpoint: The primary endpoint or coronary revascularization or non-coronary revascularization or limb amputation.
Met-HeFT: Met-HeFT secondary endpoint: 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: Met-HeFT secondary endpoint:
Extended clinical endpoint (first event analysis): The primary endpoint or coronary revascularization or non-coronary revascularization or limb amputation.Met-HeFT secondary endpoint: Death Through study completion, an average of 4 years Death
Met-HeFT secondary endpoint: 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 Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure
Met-HeFT secondary endpoint: Acute myocardial infarction Through study completion, an average of 4 years Acute myocardial infarction
Met-HeFT secondary endpoint: Stroke Through study completion, an average of 4 years Stroke
Met-HeFT secondary endpoint: New onset type 2 diabetes Through study completion, an average of 4 years New onset type 2 diabetes
Met-HeFT secondary endpoint: Hospitalization or death caused by lactic acidosis. Through study completion, an average of 4 years Hospitalization or death caused by lactic acidosis.
Met-HeFT: All-cause, total (first and subsequent) hospitalizations Through study completion, an average of 4 years Any hospitalization
Met-HeFT: Change in NT-proBNP from baseline to final follow-up Through study completion, an average of 4 years Change in NT-proBNP
Trial Locations
- Locations (25)
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
Hvidovre Hospital
🇩🇰Copenhagen, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Sydvestjysk Sygehus, Esbjerg
🇩🇰Esbjerg, Denmark
Glostrup Hospital
🇩🇰Copenhagen, Denmark
Nordsjællands Hospital Hillerød
🇩🇰Hillerød, Denmark
Regionshospital Nordjylland, Hjørring
🇩🇰Hjørring, Denmark
Herlev Hospital
🇩🇰Copenhagen, Denmark
Herning Hospital
🇩🇰Herning, 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, Denmark