ALIVE Trial: How Is This Trial Design Different?

  • C. M. Pratt
Conference paper


The development of the ALIVE study design is based upon an analysis of previous studies attempting pharmacologic reduction of arrhythmic death after acute myocardial infarction (MI). Historically, antiarrhythmic agents with predominant class I or class III (Vaughan Williams classification) activity have been tested and shown in several post-MI clinical trials to be ineffective, or even harmful, in terms of excessive morbidity and mortality because of proarrhythmic effects or end-organ toxicities [1–6]. Examples of such agents and trials include flecainide and encainide in Cardiac Arrhythmia Suppression Trial (CAST) [1], moricizine in CAST II [2], D-sotalol in the Survival With Oral D-Sotalol (SWORD) trial [3, 4], and amiodarone in the European Myocardial Infarction Amiodarone Trial (EMIAT) [5] and the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT) [6]. A significant contributing factor to the failures in many of these clinical trials was patient selection. A broad net of patients were enrolled in these studies; even those at low risk for arrhythmic death were included and thus subjected to the potentially adverse effects of these agents. This resulted in antiarrhythmic therapy in a subset of patients in whom no benefit could be gained by exposure to the drug and, in many cases, in whom there was an increased risk of mortality due to drug-related arrhythmogenicity or nonarrhythmic toxicity.


Heart Rate Variability Left Ventricular Ejection Fraction Sudden Cardiac Death Antiarrhythmic Agent Arrhythmic Death 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Echt DS, Leibson PR, Mitchell B, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, Huther ML, Richardson DW, and the CAST Investigators (1991) Mortality and morbidity in patients receiving encainide, flecainide, or placebo. N Engl J Med 324:781–788PubMedCrossRefGoogle Scholar
  2. 2.
    The Cardiac Arrhythmia Suppression Trial II Investigators (1992) Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med 327:227–233CrossRefGoogle Scholar
  3. 3.
    Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pitt B, Pratt CM, Rodda BE, Schwartz PJ, for the SWORD Investigators (1995) The SWORD trial. Survival with oral D-sotalol in patients with left ventricular dysfunction after myocardial infarction: rationale, design and methods. Am J Cardiol 75:1023–1027PubMedCrossRefGoogle Scholar
  4. 4.
    Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP, for the SWORD Investigators (1996) Effect of D-sotalol on mortality in patients with left ventricular dysfunction after myocardial infarction. Lancet 348:7–12PubMedCrossRefGoogle Scholar
  5. 5.
    Julian DG, Camm AJ, Fragin G, Janse MJ, Munoz A, Schwartz PJ, Simon P, for the European Myocardial Infarct Amiodarone Trial Investigators (1997) Randomized trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 349:667–674PubMedCrossRefGoogle Scholar
  6. 6.
    Cairns JA, Connolly SJ, Robert R, Gent M, for the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators (1997) Randomized trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Lancet 349:675–682PubMedCrossRefGoogle Scholar
  7. 7.
    Camm AJ, Karam R, Pratt CM (1998) The azimilide post-infarct survival evaluation (ALIVE) trial. Am J Cardiol 81:35D-39DPubMedCrossRefGoogle Scholar
  8. 8.
    Pratt CM, Greenway PS, Schoenfeld MH, Hibben ML, Reiffei JA (1996) An exploration of the precision of classifying sudden cardiac death: implications for the interpretation of clinical trials. Circulation 93:519-524PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2000

Authors and Affiliations

  • C. M. Pratt
    • 1
  1. 1.Section of Cardiology, Department of MedicineBaylor College of MedicineHoustonUSA

Personalised recommendations