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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 1,116
- Locations
- 7
- Primary Endpoint
- All cause mortality
Study Overview
Brief Summary
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.
Detailed Description
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.
Indication: Prevention of mortality in patients at risk of sudden death.
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 cardiovascular death as well as sudden death.
Study design: Randomized, unblinded, controlled, parallel two group trial.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •≥ 18 years of age at the time of screening.
- •Documented non-ischemic HF with an LVEF ≤ 35%.
- •NYHA class II-III. If patients are planned for an implantation with a biventricular pacemaker NYHA class IV patients will be accepted for the trial.
- •Before any study-specific procedure, including assessments for screening, the appropriate written informed consent must be obtained (see section 12.1).
- •NT-proBNP above 200 pg/ml (see appendix D).
Exclusion Criteria
- •To be eligible for this study, subjects must not meet any of the following criteria:
- •Uncorrected congenital heart disease or valve obstruction, obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism, adrenal insufficiency, active vasculitis due to collagen vascular disease.
- •On the urgent waiting list for a heart transplant (UNOS category 1A or 1B, or equivalent). Patients on the non-urgent waiting list for a heart transplant (UNOS category 2 or 7, or equivalent) are eligible for inclusion in the study.
- •Recipient of any major organ transplant (eg, lung, liver, heart or kidney).
- •Receiving or has received cytotoxic or cytostatic chemotherapy and/or radiation therapy for treatment of a malignancy within 6 month before randomisation or clinical evidence of current malignancy, with the following exceptions: basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, prostate cancer (if stable localized disease, with a life expectancy of > 2.5 years in the opinion of the investigator).
- •Known to be human immunodeficiency virus positive with an expected survival of less than 5 years due to HIV.
- •Renal failure treated with dialysis.
- •Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report
- •Any condition (eg, psychiatric illness) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
- •Unwilling to participate.
Outcomes
Primary Outcomes
All cause mortality
Time Frame: 5 years
All cause mortality
Secondary Outcomes
- Cardiovascular death(5 years)
- Quality of Life - Minnesota Living with Heart Failure Questionnaire(5 years)
- Sudden death(5 years)