Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
Information source: National Heart, Lung, and Blood Institute (NHLBI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Arrhythmia; Cardiovascular Diseases; Heart Arrest; Heart Diseases; Myocardial Infarction; Ventricular Fibrillation
Intervention: amiodarone (Drug); imipramine (Drug); mexiletine (Drug); procainamide (Drug); propafenone (Drug); quinidine (Drug); sotalol (Drug)
Phase: Phase 3
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Official(s) and/or principal investigator(s):
H. Greene, Affiliation: University of Washington
To compare the efficacy of amiodarone to conventional anti-arrhythmic therapy in individuals
who had survived one episode of out-of-hospital cardiac arrest.
Study design: Prevention, Randomized, Parallel Assignment
Sudden cardiac death can usually be attributed to the occurrence of the cardiac arrhythmia,
ventricular fibrillation. Although a significant proportion of patients experiencing sudden
cardiac death may be successfully resuscitated without disabling sequelae, this event tends
to recur. Recurrent sudden cardiac death is more common among patients demonstrating certain
clinical characteristics such as: ventricular fibrillation occurring in a setting of a remote
prior transmural infarction; the presence of abnormal left ventricular function; male gender;
concurrent complex ventricular arrhythmias identified by electrocardiographic monitoring;
extensive coronary artery disease; and the ability to induce ventricular arrhythmias
following electrical stimulation.
Multiple therapeutic approaches are offered to patients surviving primary ventricular
fibrillation. In those with evidence of myocardial ischemia, coronary revascularization
procedures may be employed. Pharmacological therapy with anti-arrhythmic agents either alone
or in combination with selection guided by the results of continuous electrocardiographic
monitoring or electrophysiologic studies is often the initial step. For those patients
refractory to medical therapy, ventricular resection or implantation of pacemakers has been
Amiodarone, a unique antiarrhythmic agent with complex pharmacokinetics and substantial
potential toxicity, has been utilized when other antiarrhythmic agents failed. The agent was
released as an oral agent for the treatment of ventricular fibrillation in the United States
by the FDA. Several investigations suggested that amiodarone was efficacious in the
treatment of ventricular fibrillation when other available agents had failed.
Patients were stratified by presence or absence of coronary artery disease, left ventricular
function, and presence or absence of drug failure prior to randomization. All patients
underwent an evaluation of left ventricular ejection fraction, usually by radionuclide
ventriculography, and baseline drug-free Holter recording or electrophysiologic study, or
both. A total of 113 patients were randomized to amiodarone and 115 patients to conventional
therapy with other antiarrhythmic agents which included procainamide, quinidine,
disopyramide, tocainide, mexiletine, encainide, flecainide, propafenone, moricizine, or
combination therapy in that order. Holter exams were given at one, three, six, twelve,
twenty-four, and thirty-six months. Patients were followed for one to five years, with an
average of three years overall. Primary endpoints for the study included in the term
'cardiac survival' were cardiac mortality, resuscitated cardiac arrest due to documented
ventricular fibrillation, and complete syncope followed by a shock from an automated
implanted defibrillator. These endpoints included sudden arrhythmic cardiac death,
resuscitated out-of-hospital ventricular fibrillation, and nonarrhythmic cardiac death. A
patient death due to amiodarone pulmonary toxicity was also considered a primary endpoint.
Minimum age: 18 Years.
Maximum age: 75 Years.
Men and women with ventricular fibrillation who had survived an out-of-hospital cardiac
arrest not associated with a Q-wave acute myocardial infarction.
Locations and Contacts
[No authors listed] Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (the CASCADE study). Am J Cardiol. 1991 Mar 15;67(7):578-84.
Greene HL. Sudden arrhythmic cardiac death--mechanisms, resuscitation and classification: the Seattle perspective. Am J Cardiol. 1990 Jan 16;65(4):4B-12B. Review.
Poole JE, Mathisen TL, Kudenchuk PJ, McAnulty JH, Swerdlow CD, Bardy GH, Greene HL. Long-term outcome in patients who survive out of hospital ventricular fibrillation and undergo electrophysiologic studies: evaluation by electrophysiologic subgroups. J Am Coll Cardiol. 1990 Sep;16(3):657-65.
Dolack GL, Callahan DB, Bardy GH, Greene HL. Signal-averaged electrocardiographic late potentials in resuscitated survivors of out-of-hospital ventricular fibrillation. Am J Cardiol. 1990 May 1;65(16):1102-4.
Bardy GH, Allen MD, Mehra R, Johnson G, Feldman S, Greene HL, Ivey TD. Transvenous defibrillation in humans via the coronary sinus. Circulation. 1990 Apr;81(4):1252-9.
Bardy GH, Troutman C, Johnson G, Mehra R, Poole JE, Dolack GL, Kudenchuk PJ, Gartman DM. Electrode system influence on biphasic waveform defibrillation efficacy in humans. Circulation. 1991 Aug;84(2):665-71.
[No authors listed] Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study). The CASCADE Investigators. Am J Cardiol. 1993 Aug 1;72(3):280-7.
Dolack GL. Clinical predictors of implantable cardioverter-defibrillator shocks (results of the CASCADE trial). Cardiac Arrest in Seattle, Conventional versus Amiodarone Drug Evaluation. Am J Cardiol. 1994 Feb 1;73(4):237-41.
Greene HL. The CASCADE Study: randomized antiarrhythmic drug therapy in survivors of cardiac arrest in Seattle. CASCADE Investigators. Am J Cardiol. 1993 Nov 26;72(16):70F-74F.
Maynard C. Rehospitalization in surviving patients of out-of-hospital ventricular fibrillation (the CASCADE Study). Cardiac Arrest in Seattle: Conventional Amiodarone Drug Evaluation. Am J Cardiol. 1993 Dec 1;72(17):1295-300.
Starting date: April 1987
Last updated: June 23, 2005