Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000526
Status:
COMPLETED
Last Update Posted:
2016-05-06
First Post:
1999-10-27
Brief Title:
Cardiac Arrhythmia Suppression Trial CAST
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2004-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine whether drug treatment of asymptomatic ventricular arrhythmias in post-myocardial infarction patients reduced the incidence of sudden cardiac death and total mortality
Detailed Description:
BACKGROUND
Each year over 400000 people in the United States die suddenly of coronary heart disease The majority have known coronary heart disease Of these the post-myocardial infarction population constitutes a large proportion About 8 to 15 percent of patients who recover from an acute myocardial infarction die in the subsequent year Half of these deaths are usually sudden presumably due to arrhythmia Advanced age poor ventricular function and presence of ventricular arrhythmias can identify post-MI patients at high risk of sudden cardiac death and all-cause mortality
A number of clinical trials have evaluated whether acute or chronic anti-arrhythmic drug therapy can reduce mortality in post-MI patients Of these only the use of acute intravenous and long-term beta-blockers independently and in combination had been shown to reduce mortality However beta-blockers have many actions in addition to being anti-arrhythmic agents and it is possible that these other effects may have been particularly important in prolonging life
None of the clinical trials of other antiarrhythmic drugs had shown significant benefits from treatment and a number had even failed to show a positive trend It was certainly possible that treatment of ventricular premature depolarizations in itself did not lead to a reduction in mortality or even sudden death The studies that had been done however had not adequately addressed the issue Most of the studies were small and did not select patients on the basis of frequent ectopic beats Moreover appropriate drugs in optimal doses may not have been used and adverse effects may well have outweighed any potential benefit Poor compliance perhaps due to adverse effects may also have limited the opportunity for a beneficial outcome
In an effort to address some of these points the National Heart Lung and Blood Institute initiated the Cardiac Arrhythmia Pilot Study in 1982 The objectives were to assess whether post-MI patients with documented ventricular arrhythmia could be identified and enrolled into a double-blind clinical trial whether one or more drugs could be found to effectively and safely reduce ventricular premature depolarizations over a one-year period whether dose-adjustment could be carried out using ambulatory ECGs and whether good patient compliance could be maintained The Cardiac Arrhythmia Pilot Study which enrolled 500 patients evaluated four active drugs encainide ethmozine flecainide imipramine against placebo The study was too small to determine whether any of these drugs had an effect on mortality or major morbidity The study was completed in July 1986
The pilot study demonstrated that patient recruitment was feasible that dose-adjustment could be accomplished and that good compliance to the protocol could be achieved Because of the encouraging results of the pilot study the NHLBI conducted a full-scale trial
DESIGN NARRATIVE
Randomized double-blind Enrollment began in June 1987 when twenty-seven clinical centers began to randomize 4400 post-myocardial infarction patients to placebo or treatment with encainide flecainide or moricizine Prior to actual randomization there was an open-label titration period to identify patients who responded to treatment A total of 1727 patients who responded were randomized 1455 to encainide flecainide or placebo and 272 to moricizine or placebo In April 1989 encainide and flecainide were discontinued because of increased total mortality and sudden arrhythmic death CAST continued to compare moricizine to placebo in 1300 patients for 18 months until August 1991 when the moricizine portion of the trial was stopped early because of excess deaths The primary outcome variable in the full-scale trial was sudden cardiac death with total mortality a secondary endpoint Data analysis continued through March 1998
Each year over 400000 people in the United States die suddenly of coronary heart disease The majority have known coronary heart disease Of these the post-myocardial infarction population constitutes a large proportion About 8 to 15 percent of patients who recover from an acute myocardial infarction die in the subsequent year Half of these deaths are usually sudden presumably due to arrhythmia Advanced age poor ventricular function and presence of ventricular arrhythmias can identify post-MI patients at high risk of sudden cardiac death and all-cause mortality
A number of clinical trials have evaluated whether acute or chronic anti-arrhythmic drug therapy can reduce mortality in post-MI patients Of these only the use of acute intravenous and long-term beta-blockers independently and in combination had been shown to reduce mortality However beta-blockers have many actions in addition to being anti-arrhythmic agents and it is possible that these other effects may have been particularly important in prolonging life
None of the clinical trials of other antiarrhythmic drugs had shown significant benefits from treatment and a number had even failed to show a positive trend It was certainly possible that treatment of ventricular premature depolarizations in itself did not lead to a reduction in mortality or even sudden death The studies that had been done however had not adequately addressed the issue Most of the studies were small and did not select patients on the basis of frequent ectopic beats Moreover appropriate drugs in optimal doses may not have been used and adverse effects may well have outweighed any potential benefit Poor compliance perhaps due to adverse effects may also have limited the opportunity for a beneficial outcome
In an effort to address some of these points the National Heart Lung and Blood Institute initiated the Cardiac Arrhythmia Pilot Study in 1982 The objectives were to assess whether post-MI patients with documented ventricular arrhythmia could be identified and enrolled into a double-blind clinical trial whether one or more drugs could be found to effectively and safely reduce ventricular premature depolarizations over a one-year period whether dose-adjustment could be carried out using ambulatory ECGs and whether good patient compliance could be maintained The Cardiac Arrhythmia Pilot Study which enrolled 500 patients evaluated four active drugs encainide ethmozine flecainide imipramine against placebo The study was too small to determine whether any of these drugs had an effect on mortality or major morbidity The study was completed in July 1986
The pilot study demonstrated that patient recruitment was feasible that dose-adjustment could be accomplished and that good compliance to the protocol could be achieved Because of the encouraging results of the pilot study the NHLBI conducted a full-scale trial
DESIGN NARRATIVE
Randomized double-blind Enrollment began in June 1987 when twenty-seven clinical centers began to randomize 4400 post-myocardial infarction patients to placebo or treatment with encainide flecainide or moricizine Prior to actual randomization there was an open-label titration period to identify patients who responded to treatment A total of 1727 patients who responded were randomized 1455 to encainide flecainide or placebo and 272 to moricizine or placebo In April 1989 encainide and flecainide were discontinued because of increased total mortality and sudden arrhythmic death CAST continued to compare moricizine to placebo in 1300 patients for 18 months until August 1991 when the moricizine portion of the trial was stopped early because of excess deaths The primary outcome variable in the full-scale trial was sudden cardiac death with total mortality a secondary endpoint Data analysis continued through March 1998
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: