Danish ICD Study in Patients With Dilated Cardiomyopathy (DANISH)

July 16, 2019 updated by: Danish Study Group

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

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 in patients with heart failure of non-ischemic oetiology.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 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 ethiology 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.

Screening and Randomisation: After the signing of informed consent, screening will include medical history, vital signs, physical exam, blood chemistry, haematology, and NT-proBNP. 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. An Endpoint Classification Committee will adjudicate hospitalizations and deaths for causality.

An independent Data Monitoring Committee will periodically review mortality data throughout the study.

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. For each treatment group, Kaplan-Meier curves will be estimated, graphically displayed, and compared using a logrank test. A covariate-adjusted analysis of the primary endpoint using a Cox proportional hazards model will be performed as a supportive analysis. The hazard ratio and its corresponding 95% confidence interval will be estimated. Subjects withdrawing from the study early (other than for withdrawal of consent) will be followed for potential development of the primary endpoint. Subjects completing the study and not experiencing the composite event will be censored.

Secondary Endpoint Analysis: All time-to-event secondary endpoints will be analyzed similarly to the primary endpoint.

Sample Size: Hazard rates have been estimated for the placebo and ICD groups using subjects from a variety of databases (including the Echos database and the publication of Definite). Assuming a 24-month enrollment period and a 36 month follow-up period (resulting in a 5-year study with a minimum treatment period of 3 years and approximately a median survival time of 60 months), a total of 812 subjects will provide a 80% power with a 2-sided significance level of 5% for detecting a reduction in hazard of 25%.

Safety Summary: The subject incidence of adverse events will be tabulated for each group. Adverse events related to ICD implantation will be summarized. During the trial inappropriate shocks will be summarized.

Data Monitoring Committee: An independent Data Monitoring Committee consisting of members with relevant expertise will be assembled prior to study commencement. This committee will periodically review safety data.

Endpoint Classification Committee: An external Endpoint Classification Committee will adjudicate death as sudden or non-sudden throughout the study.

Study Type

Interventional

Enrollment (Actual)

1116

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet, University of Copenhagen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: B
Other: Optimal medical treatment
ACE-inhibitors or ARB Beta-blocker Optional aldosterone antagonist
Experimental: A
Heart Failure nonischemic ethiology
Device: ICD
Implantation of an ICD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
All cause mortality
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Quality of Life and health economics
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Danish Study Group

Collaborators

Danish Heart Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2008

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

October 11, 2007

First Submitted That Met QC Criteria

October 11, 2007

First Posted (Estimate)

October 12, 2007

Study Record Updates

Last Update Posted (Actual)

July 18, 2019

Last Update Submitted That Met QC Criteria

July 16, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Danish-ICD-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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