Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
Condition: Arrhythmia; Cardiovascular Diseases; Heart Arrest; Heart Diseases; Myocardial Infarction; Ventricular Fibrillation
MeSH terms: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Heart Arrest; Ventricular Fibrillation; Infarction
Study type: Interventional
Phase: Phase 3

Summary: 
      To compare the efficacy of amiodarone to conventional anti-arrhythmic therapy in individuals
      who had survived one episode of out-of-hospital cardiac arrest.
    

Detailed description: 
      BACKGROUND:

      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
      employed.

      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.

      DESIGN NARRATIVE:

      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.
    

Intervention name(s): amiodarone; imipramine; mexiletine; procainamide; propafenone; quinidine; sotalol
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Quinidine; Amiodarone; Sotalol; Propafenone; Mexiletine; Procainamide; Imipramine
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Prevention