Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00541268 |
| Other study ID # |
2007-005606-45 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 2008 |
| Est. completion date |
July 2016 |
Study information
| Verified date |
July 2019 |
| Source |
Danish Study Group |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
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.
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.
As event rate was lower than expected the steering committee decided to prolong follow-up and
increase sample size slightly to 1150 patients. Secondly, the steering comittee decided to
add cardiovascular death as a secondary outcome.
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.
