Efficacy of Implantable Cardioverter Defibrillator in Patients With Non-ischemic Systolic Heart Failure on Mortality (DANISH)
Primary objective: The primary objective of this study is to determine the efficacy of ICD therapy compared with control on the endpoint of death from any cause.
Secondary objective: The secondary objectives of the study are to determine if ICD therapy reduces sudden death.
Study design: Randomized, unblinded, controlled, parallel two group trial.
Primary endpoint: Time to death from any cause.
Sample size: In total, 1000 patients with 500 receiving ICD and 500 patients constituting the control group.
Summary of Subject Eligibility Criteria: Patients with clinical heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, non-ischemic etiology and NT-proBNP above 200 pg/ml. Patients in NYHA class IV will only be randomised if also fulfilling criteria for a biventricular pacemaker.
Control group: Patients receiving standard therapy for heart failure including ACE-inhibitor/Angiotensin-Receptor-Blocker and Betablocker unless not tolerated. Aldosterone antagonism is optional.
Study Duration: The study comprises a screening period of up to 2 years, followed by a treatment phase of a minimum of 36 months.
Randomisation: After fulfilling all eligibility criteria, subjects will be randomized 1:1 to receive ICD implantation or continue usual control. Randomisation will be stratified according to treatment with a biventricular pacemaker.
Treatment: After randomisation patients allocated to ICD treatment should receive this as fast as possible and preferably within 2 weeks (latest 4 weeks). The ICD will be programmed with anti-tachycardia pacing and shock therapy.
Assessments: Deaths and hospitalisations for heart failure, stroke or arrhythmias will be recorded throughout the study duration.
Statistical Considerations: Median lifetime in the control group is expected to be 5 years. A p-value of 5% (2-sided) is required for significance together with a power of at least 80%. With a relative risk reduction of 25% a sample size of 812 patients in total is required. In order to allow for cross-over a sample size of 1000 is planned.
Primary Endpoint Analysis: The principal analysis for the primary endpoint (time to death from any cause) will employ the intent-to-treat principle and use a survival analysis.
Secondary Endpoint Analysis: All time-to-event secondary endpoints will be analyzed similarly to the primary endpoint.
Other: Optimal medical treatment
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A DANish Randomized, Controlled, Multicenter Study to Assess the Efficacy of Implantable Cardioverter Defibrillator in Patients With Non-ischemic Systolic Heart Failure on Mortality. The DANISH Study|
- All cause mortality [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
- Cardiovascular death [ Time Frame: all time ] [ Designated as safety issue: No ]
- Sudden death [ Time Frame: all time ] [ Designated as safety issue: No ]
- Quality of Life [ Time Frame: all time ] [ Designated as safety issue: No ]Patient reported outcome thru heart failure questionnaires
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Heart Failure nonischemic etiology
Intracardioverter defibrillators from 2 different manufacturers
|Active Comparator: B||
Other: Optimal medical treatment
ACEi or angiotensin receptor blockers Betablockers Aldosterone blockers
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00541268
|Rigshospitalet, University of Copenhagen|
|Copenhagen, Denmark, 2100|
|Copenhagen, Denmark, 2900|
|Odense, Denmark, 5000|
|Study Chair:||Lars Køber, MD, D.Sci||Department of Cardiology, Rigshospitalet.|