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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002150-12 | EudraCT Number |
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| Name | Class |
|---|---|
| Danish Heart Foundation | OTHER |
| Danish Council for Independent Research | OTHER |
| The Danish Regions: Foundation for Medical Research | UNKNOWN |
| The Novo Nordisk Foundation |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydralazine Isosorbide Dinitrate | Drug | Tablet BiDil (Hydralazine 37.5 mg/ Isosorbide Dinitrate (ISDN) 20 mg) 2 tablets x 3 daily |
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| Measure | Description | Time Frame |
|---|---|---|
| H-HeFT combined primary endpoint | 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. | Through study completion, an average of 4 years |
| Met-HeFT combined primary endpoint | 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 | Through study completion, an average of 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| H-HeFT Death | Death | Through study completion, an average of 4 years |
| H-HeFT: Heart failure events | Hospitalization with worsening heart failure or urgent visit resulting in intravenous therapy or metolazone therapy for heart failure or heart transplantation or implantation of LVAD |
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Inclusion Criteria:
General inclusion criteria for both H-HeFT and Met-HeFT
Specific inclusion criteria for only H-HeFT:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Henrik Wiggers, MD, PhD | Dept. of Cardiology, Aarhus University Hospital, Aarhus, Denmark | Study Chair |
| Lars Køber, MD, PhD | Dept. of Cardiology, Rigshospitalet, Copenhagen, Denmark | Study Chair |
| Finn Gustafsson, MD, PhD | Dept. of Cardiology, Rigshospitalet, Copenhagen, Denmark | Principal Investigator |
| Søren Mellemkjaer, MD, PhD | Dept. of Cardiology, Aarhus University Hospital, Aarhus, Denmark | Principal Investigator |
| Gunnar Gislason, MD, PhD | The Danish Heart Foundation, Copenhagen, Denmark | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Holbæk Hospital | Holbæk | Region Sjælland | Denmark | |||
| Sygehus Sønderjylland, Aabenraa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33039340 | Derived | Wiggers H, Kober L, Gislason G, Schou M, Poulsen MK, Vraa S, Nielsen OW, Bruun NE, Norrelund H, Hollingdal M, Barasa A, Bottcher M, Dodt K, Hansen VB, Nielsen G, Knudsen AS, Lomholdt J, Mikkelsen KV, Jonczy B, Bronnum-Schou J, Poenaru MP, Abdulla J, Raymond I, Mahboubi K, Sillesen K, Serup-Hansen K, Madsen JS, Kristensen SL, Larsen AH, Botker HE, Torp-Petersen C, Eiskjaer H, Moller J, Hassager C, Steffensen FH, Bibby BM, Refsgaard J, Hofsten DE, Mellemkjaer S, Gustafsson F. The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 x 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT). Am Heart J. 2021 Jan;231:137-146. doi: 10.1016/j.ahj.2020.09.020. Epub 2020 Oct 9. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 9, 2026 | Jun 9, 2026 |
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| UNKNOWN |
| The Aase og Ejnar Danielsen Foundation | UNKNOWN |
Patients can be allocated to either
Patient characteristics are entered in an electronic CRF. According to in- and exclusion criteria they are randomized in three blocks:
Analysis will be performed in:
The study is event driven. Anticipated: both H-HeFT and Met-HeFT 900, only H-HeFT 400, only Met-HeFT 200 patients.
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| Placebo Oral Tablet | Drug | 2 tablets x 3 daily |
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| Metformin Hydrochloride | Drug | Tablet Metformin hydrochloride 500 mg 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily) |
|
| Placebo Oral Tablet | Drug | 2 tablets x 2 daily (eGFR 35-60 ml/min: 500 mg x 2 daily) |
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| Through study completion, an average of 4 years |
| H-HeFT: Death or cardiovascular hospitalization | 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 or or heart transplantation or implantation of LVAD | Through study completion, an average of 4 years |
| H-HeFT combined primary endpoint of total (first and recurrent) events | Composite of total (first and recurrent) events in the primary 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. | Through study completion, an average of 4 years |
| H-HeFT: All-cause, total (first and subsequent) hospitalizations | Any hospitalization | Through study completion, an average of 4 years |
| H-HeFT: Change in NT-proBNP from baseline to final follow-up | Change in NT-proBNP from baseline to final follow-up | Through study completion, an average of 4 years |
| H-HeFT: Cardiovascular hospitalizations | Any cardiovascular hospitalization | Through study completion, an average of 4 years |
| Met-HeFT combined endpoint of total (first and recurrent) events in the primary endpoint | 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 | Through study completion, an average of 4 years |
| Met-HeFT secondary endpoint: Death | 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 | 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. | 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 | Acute myocardial infarction | Through study completion, an average of 4 years |
| Met-HeFT secondary endpoint: Stroke | Stroke | Through study completion, an average of 4 years |
| Met-HeFT secondary endpoint: New onset type 2 diabetes | New onset type 2 diabetes | Through study completion, an average of 4 years |
| Met-HeFT secondary endpoint: Hospitalization or death caused by lactic acidosis. | Hospitalization or death caused by lactic acidosis. | Through study completion, an average of 4 years |
| Met-HeFT: All-cause, total (first and subsequent) hospitalizations | Any hospitalization | Through study completion, an average of 4 years |
| Met-HeFT: Change in NT-proBNP from baseline to final follow-up | Change in NT-proBNP | Through study completion, an average of 4 years |
| Met-HeFT: Cardiovascular hospitalizations | Any cardiovascular hospitalization | Through study completion, an average of 4 years |
| 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 | Denmark |
| SAP_001.pdf |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D003920 | Diabetes Mellitus |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| C431665 | isosorbide-hydralazine combination |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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