Cardiovascular DiseasesPhase 3NCT00000526
Cardiac Arrhythmia Suppression Trial (CAST)
A Phase 3 study testing encainide, flecainide and moricizine in people with Cardiovascular Diseases and Coronary Disease, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cardiovascular Diseases, Coronary Disease, Death, Sudden, Cardiac
- What is being tested?
- encainide, flecainide and moricizine
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Aug 1986to Mar 1998
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Men and women with ventricular premature depolarization six days to two years after the start of myocardial infarction.
About this study
To determine whether drug treatment of asymptomatic ventricular arrhythmias in post-myocardial infarction patients reduced the incidence of sudden cardiac death and total mortality.
Read the detailed description
BACKGROUND:
Each year over 400,000 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 ECG's; 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 4,400 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 1,727 patients who responded were randomized: 1,455 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 1,300 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.
- Conditions
- Cardiovascular Diseases, Coronary Disease, Death, Sudden, Cardiac, Heart Arrest, Heart Diseases, Myocardial Infarction
- Being tested
- encainide, flecainide, moricizine
- Medical subject headings
- Cardiovascular Diseases, Coronary Disease, Death, Sudden, Cardiac, Heart Arrest, Heart Diseases, Myocardial Infarction, Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
encainideDrug
flecainideDrug
moricizineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 1999 (estimated)
- Study startAug 1986
- Study completionMar 1998
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (56)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Alfred Hallstrom, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000526
- Sponsor's protocol ID
- 45
- Status last verified
- Aug 2004
- First submitted
- 27 Oct 1999
- Last updated
- 6 May 2016
- Results posted
- No
Publications
Pratt CM, Moye LA. The cardiac arrhythmia suppression trial. Casting suppression in a different light. Circulation. 1995 Jan 1;91(1):245-7. doi: 10.1161/01.cir.91.1.245. No abstract available.
PubMed 7805210el-Sherif N, Denes P, Katz R, Capone R, Mitchell LB, Carlson M, Reynolds-Haertle R. Definition of the best prediction criteria of the time domain signal-averaged electrocardiogram for serious arrhythmic events in the postinfarction period. The Cardiac Arrhythmia Suppression Trial/Signal-Averaged Electrocardiogram (CAST/SAECG) Substudy Investigators. J Am Coll Cardiol. 1995 Mar 15;25(4):908-14. doi: 10.1016/0735-1097(94)00504-j.
PubMed 7884096Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989 Aug 10;321(6):406-12. doi: 10.1056/NEJM198908103210629.
PubMed 2473403Bigger JT Jr. The events surrounding the removal of encainide and flecainide from the Cardiac Arrhythmia Suppression Trial (CAST) and why CAST is continuing with moricizine. J Am Coll Cardiol. 1990 Jan;15(1):243-5. doi: 10.1016/0735-1097(90)90209-8. No abstract available.
PubMed 2104884Morganroth J, Bigger JT Jr, Anderson JL. Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available. Am J Cardiol. 1990 Jan 1;65(1):40-8. doi: 10.1016/0002-9149(90)90023-t.
PubMed 1688481Pratt CM, Moye LA. The Cardiac Arrhythmia Suppression Trial: background, interim results and implications. Am J Cardiol. 1990 Jan 16;65(4):20B-29B. doi: 10.1016/0002-9149(90)91287-g.
PubMed 2105049Pratt CM. The Cardiac Arrhythmia Suppression Trial. Introduction: The aftermath of the CAST--a reconsideration of traditional concepts. Am J Cardiol. 1990 Jan 16;65(4):1B-2B. doi: 10.1016/0002-9149(90)91283-c. No abstract available.
PubMed 2404392Pratt CM, Brater DC, Harrell FE Jr, Kowey PR, Leier CV, Lowenthal DT, Messerli F, Packer M, Pritchett EL, Ruskin JN. Clinical and regulatory implications of the Cardiac Arrhythmia Suppression Trial. Am J Cardiol. 1990 Jan 1;65(1):103-5. doi: 10.1016/0002-9149(90)90034-x. No abstract available.
PubMed 1688479Pratt CM, Moye L. The cardiac arrhythmia suppression trial: implications for antiarrhythmic drug development. J Clin Pharmacol. 1990 Nov;30(11):967-74. doi: 10.1002/j.1552-4604.1990.tb03580.x. No abstract available.
PubMed 2122983Bigger JT Jr. Implications of the Cardiac Arrhythmia Suppression Trial for antiarrhythmic drug treatment. Am J Cardiol. 1990 Feb 20;65(8):3D-10D; discussion 68D-71D. doi: 10.1016/0002-9149(90)91410-8.
PubMed 2106253Morganroth J, Bigger JT Jr. Pharmacologic management of ventricular arrhythmias after the cardiac arrhythmia suppression trial. Am J Cardiol. 1990 Jun 15;65(22):1497-503. doi: 10.1016/0002-9149(90)91362-a. No abstract available.
PubMed 2091621Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991 Mar 21;324(12):781-8. doi: 10.1056/NEJM199103213241201.
PubMed 1900101Epstein AE, Bigger JT Jr, Wyse DG, Romhilt DW, Reynolds-Haertle RA, Hallstrom AP. Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled. J Am Coll Cardiol. 1991 Jul;18(1):14-9. doi: 10.1016/s0735-1097(10)80210-4.
PubMed 1904891Wyse DG, Hallstrom A, McBride R, Cohen JD, Steinberg JS, Mahmarian J. Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy. J Am Coll Cardiol. 1991 Jul;18(1):20-8. doi: 10.1016/s0735-1097(10)80211-6.
PubMed 1904892Hallstrom AP, Verter J, Friedman L. Randomizing responders. Cardiac Arrhythmia Suppression Trial (CAST) investigators. Control Clin Trials. 1991 Aug;12(4):486-503. doi: 10.1016/0197-2456(91)90009-b.
PubMed 1657526
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Arrhythmia Suppression Trial (CAST)
- ClinicalTrials.gov ID
- NCT00000526
- Acronym / sponsor ID
- 45
- Conditions
- Cardiovascular Diseases, Coronary Disease, Death, Sudden, Cardiac, Heart Arrest, Heart Diseases, Myocardial Infarction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Aug 1986
- Study completion
- Mar 1998
- First posted
- 28 Oct 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 400,000 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 ECG's; 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 4,400 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 1,727 patients who responded were randomized: 1,455 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 1,300 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| encainide | Drug | – |
| flecainide | Drug | – |
| moricizine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2016.
- Background: PubMed 7805210Pratt CM, Moye LA. The cardiac arrhythmia suppression trial. Casting suppression in a different light. Circulation. 1995 Jan 1;91(1):245-7. doi: 10.1161/01.cir.91.1.245. No abstract available.
- Background: PubMed 7884096el-Sherif N, Denes P, Katz R, Capone R, Mitchell LB, Carlson M, Reynolds-Haertle R. Definition of the best prediction criteria of the time domain signal-averaged electrocardiogram for serious arrhythmic events in the postinfarction period. The Cardiac Arrhythmia Suppression Trial/Signal-Averaged Electrocardiogram (CAST/SAECG) Substudy Investigators. J Am Coll Cardiol. 1995 Mar 15;25(4):908-14. doi: 10.1016/0735-1097(94)00504-j.
- Background: PubMed 2473403Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989 Aug 10;321(6):406-12. doi: 10.1056/NEJM198908103210629.
- Background: PubMed 2104884Bigger JT Jr. The events surrounding the removal of encainide and flecainide from the Cardiac Arrhythmia Suppression Trial (CAST) and why CAST is continuing with moricizine. J Am Coll Cardiol. 1990 Jan;15(1):243-5. doi: 10.1016/0735-1097(90)90209-8. No abstract available.
- Background: PubMed 1688481Morganroth J, Bigger JT Jr, Anderson JL. Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available. Am J Cardiol. 1990 Jan 1;65(1):40-8. doi: 10.1016/0002-9149(90)90023-t.
- Background: PubMed 2105049Pratt CM, Moye LA. The Cardiac Arrhythmia Suppression Trial: background, interim results and implications. Am J Cardiol. 1990 Jan 16;65(4):20B-29B. doi: 10.1016/0002-9149(90)91287-g.
- Background: PubMed 2404392Pratt CM. The Cardiac Arrhythmia Suppression Trial. Introduction: The aftermath of the CAST--a reconsideration of traditional concepts. Am J Cardiol. 1990 Jan 16;65(4):1B-2B. doi: 10.1016/0002-9149(90)91283-c. No abstract available.
- Background: PubMed 1688479Pratt CM, Brater DC, Harrell FE Jr, Kowey PR, Leier CV, Lowenthal DT, Messerli F, Packer M, Pritchett EL, Ruskin JN. Clinical and regulatory implications of the Cardiac Arrhythmia Suppression Trial. Am J Cardiol. 1990 Jan 1;65(1):103-5. doi: 10.1016/0002-9149(90)90034-x. No abstract available.
- Background: PubMed 2122983Pratt CM, Moye L. The cardiac arrhythmia suppression trial: implications for antiarrhythmic drug development. J Clin Pharmacol. 1990 Nov;30(11):967-74. doi: 10.1002/j.1552-4604.1990.tb03580.x. No abstract available.
- Background: PubMed 2106253Bigger JT Jr. Implications of the Cardiac Arrhythmia Suppression Trial for antiarrhythmic drug treatment. Am J Cardiol. 1990 Feb 20;65(8):3D-10D; discussion 68D-71D. doi: 10.1016/0002-9149(90)91410-8.
- Background: PubMed 2091621Morganroth J, Bigger JT Jr. Pharmacologic management of ventricular arrhythmias after the cardiac arrhythmia suppression trial. Am J Cardiol. 1990 Jun 15;65(22):1497-503. doi: 10.1016/0002-9149(90)91362-a. No abstract available.
- Background: PubMed 1900101Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991 Mar 21;324(12):781-8. doi: 10.1056/NEJM199103213241201.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfred Hallstrom
University of Washington
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing encainide, flecainide and moricizine in people with Cardiovascular Diseases and Coronary Disease, run by National Heart, Lung, and Blood Institute (NHLBI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000526, which also lists 56 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2016.