Clinical trial NCT00000504: Cardiac Arrhythmia Pilot Study (CAPS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arrhythmia
Cardiovascular Diseases
Heart Diseases
Ventricular Arrhythmia
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 1999-10-28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: To compare the effectiveness of various drugs and drug combinations in suppressing complex ventricular arrhythmias, and to evaluate their safety.

Detailed description: BACKGROUND:

Epidemiologic studies had indicated that complex ventricular premature beats made an independent contribution to risk of sudden death in survivors of a myocardial infarction (MI), and did not appear to be merely a reflection of their association with relatively severe myocardial damage. The potential for reduction in mortality by identification and administration of drugs capable of safely suppressing ventricular arrhythmias was tremendous. In 1982, there was incomplete knowledge regarding which types of ventricular arrhythmias responded to various kinds of drugs. A pilot study of antiarrhythmic agents helped clarify this issue.

Numerous antiarrhythmic agents with differing pharmacologic properties and side effects had been shown to suppress ventricular arrhythmias. It had also been postulated that antiarrhythmics might raise an individual's threshold for experiencing ventricular fibrillation. There had been several published reports of large (at least l00 patients), long-term clinical trials of antiarrhythmic agents in post-MI patients. None of these had yielded statistically significant results using mortality as the response variable. This might have been due to incorrect drug selection, inadequate sample size, inappropriate choice of patients, or the lack of impact of arrhythmia treatment on mortality.

Due to incomplete knowledge as to which drug(s) and combinations of drugs were most effective, it was considered to be premature to undertake a full scale trial in 1981-1982. However, the public health problem was of sufficient magnitude to warrant a pilot study to learn more about the efficacy and safety of various antiarrhythmic drugs singly or in combination.

The protocol planning phase began in October l982. Patient recruitment started in July l983 and ended in the summer of 1985. Each patient was followed for one year.

DESIGN NARRATIVE:

Randomized, double-blind, fixed sample. A total of 502 patients were randomly assigned to 5 treatment groups consisting of encainide, ethmozine, flecainide, imipramine, and placebo.

Eligibility criteria: Men and women. Patients had acute myocardial infarction and ventricular arrhythmias.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Rochester
name: Toshio Akiyama
affiliation: Salt Lake Clinic Research Foundation
name: Allan Barker
affiliation: Columbia University
name: J. Bigger
affiliation: Rhode Island Hospital
name: Robert Capone
affiliation: Johns Hopkins University
name: Lawrence Griffith
affiliation: Baylor College of Medicine
name: Craig Pratt
affiliation: Medical College of Virginia
name: David Richardson
affiliation: University of Alabama at Birmingham
name: William Rogers
affiliation: V.A. Medical Center
name: Michael Sather
affiliation: Clinical Data, Inc
name: Israel Stein
affiliation: Montreal Heart Institute
name: Pierre Theroux
affiliation: Vanderbilt University Medical Center
name: Raymond Woosley
References:
citation: The Cardiac Arrhythmia Pilot Study. The CAPS investigators. Am J Cardiol. 1986 Jan 1;57(1):91-5. doi: 10.1016/0002-9149(86)90958-6.
citation: Recruitment and baseline description of patients in the Cardiac Arrhythmia Pilot Study. The Cardiac Arrhythmia Pilot Study (CAPS) investigators. Am J Cardiol. 1988 Apr 1;61(10):704-13. doi: 10.1016/0002-9149(88)91052-1.
citation: Cardiac Arrhythmia Pilot Study (CAPS) Investigators. Effects of encainide, flecainide, imipramine and moricizine on ventricular arrhythmias during the year after acute myocardial infarction: the CAPS. Am J Cardiol. 1988 Mar 1;61(8):501-9. doi: 10.1016/0002-9149(88)90754-0.
citation: Greene HL, Richardson DW, Barker AH, Roden DM, Capone RJ, Echt DS, Friedman LM, Gillespie MJ, Hallstrom AP, Verter J. Classification of deaths after myocardial infarction as arrhythmic or nonarrhythmic (the Cardiac Arrhythmia Pilot Study). Am J Cardiol. 1989 Jan 1;63(1):1-6. doi: 10.1016/0002-9149(89)91065-5.
citation: Greene HL, Richardson DW, Hallstrom AP, McBride R, Capone RJ, Barker AH, Roden DM, Echt DS. Congestive heart failure after acute myocardial infarction in patients receiving antiarrhythmic agents for ventricular premature complexes (Cardiac Arrhythmia Pilot Study). Am J Cardiol. 1989 Feb 15;63(7):393-8. doi: 10.1016/0002-9149(89)90306-8.
citation: Anderson JL, Hallstrom AP, Griffith LS, Ledingham RB, Reiffel JA, Yusuf S, Barker AH, Fowles RE, Young JB. Relation of baseline characteristics to suppression of ventricular arrhythmias during placebo and active antiarrhythmic therapy in patients after myocardial infarction. Circulation. 1989 Mar;79(3):610-9. doi: 10.1161/01.cir.79.3.610.
citation: Ahern DK, Gorkin L, Anderson JL, Tierney C, Hallstrom A, Ewart C, Capone RJ, Schron E, Kornfeld D, Herd JA, et al. Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS). Am J Cardiol. 1990 Jul 1;66(1):59-62. doi: 10.1016/0002-9149(90)90736-k.
citation: Follick MJ, Ahern DK, Gorkin L, Niaura RS, Herd JA, Ewart C, Schron EB, Kornfeld DS, Capone RJ. Relation of psychosocial and stress reactivity variables to ventricular arrhythmias in the Cardiac Arrhythmia Pilot Study (CAPS). Am J Cardiol. 1990 Jul 1;66(1):63-7. doi: 10.1016/0002-9149(90)90737-l.
citation: Pratt CM, Hallstrom A, Theroux P, Romhilt D, Coromilas J, Myles J. Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS). J Am Coll Cardiol. 1991 Jan;17(1):1-8. doi: 10.1016/0735-1097(91)90697-8.
citation: Hallstrom AP, Bigger JT Jr, Roden D, Friedman L, Akiyama T, Richardson DW, Rogers WJ, Waldo AL, Pratt CM, Capone RJ, et al. Prognostic significance of ventricular premature depolarizations measured 1 year after myocardial infarction in patients with early postinfarction asymptomatic ventricular arrhythmia. J Am Coll Cardiol. 1992 Aug;20(2):259-64. doi: 10.1016/0735-1097(92)90089-6.
citation: Wyse DG, Morganroth J, Ledingham R, Denes P, Hallstrom A, Mitchell LB, Epstein AE, Woosley RL, Capone R. New insights into the definition and meaning of proarrhythmia during initiation of antiarrhythmic drug therapy from the Cardiac Arrhythmia Suppression Trial and its pilot study. The CAST and CAPS Investigators. J Am Coll Cardiol. 1994 Apr;23(5):1130-40. doi: 10.1016/0735-1097(94)90601-7.
citation: Haakenson C, Akiyama T, Hallstrom A, Sather MR. Masking drug treatments in the Cardiac Arrhythmia Pilot Study (CAPS). FASHP for the CAPS Investigators. Control Clin Trials. 1996 Aug;17(4):294-303. doi: 10.1016/0197-2456(95)00195-6.