Challenges in the conduct of large simple trials of important generic questions in resource-poor settings: the CREATE and ECLA trial program evaluating GIK (glucose, insulin and potassium) and low-molecular-weight heparin in acute myocardial infarction

Am Heart J. 2004 Dec;148(6):1068-78. doi: 10.1016/j.ahj.2004.08.033.

Abstract

Background: Approximately 15.5 million deaths from cardiovascular diseases occur every year. About half are due to acute myocardial infarction (AMI), and 80% occur in low- and middle-income countries. Therefore, low-cost therapies would be invaluable. Although glucose-insulin-potassium (GIK) infusion and low-molecular-weight heparin (LMWH) appear to be promising in AMI, the available trials are inconclusive and these treatments require rigorous evaluation.

Methods: The Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment and Evaluation-Estudios Clinicos Latino America (CREATE-ECLA) study is a randomized controlled trial in ST-elevation AMI patients evaluating a 24-hour infusion of Glucose-Insulin-Potassium (GIK) intravenous vs usual care (control) on 30-day mortality in 20,000 patients from 21 countries. Patients from India and China (n = 15,000) are also randomized using a factorial design to receive low-molecular-weight heparin (Reviparin) or placebo injection twice daily for 7 days to assess the impact on the composite outcomes of death, reinfarction or stroke (first co-primary outcome) or the composite + refractory ischemia (second co-primary outcome).

Results: Twenty thousand two hundred and one (20,201) GIK/control patients and 15,570 Reviparin/placebo patients have been included, with results expected in November 2004.

Conclusions: The CREATE-ECLA trial will provide definitive answers to the role of 2 practical, promising and low-cost therapies, LMWH and GIK, in AMI patients. If effective, these therapies could be used in small medical centers in low- and middle- income countries. The experiences in this trial indicate that large trials of important questions can be successfully conducted in resource-poor settings, by academic groups without industry involvement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Protocols
  • Drug Therapy, Combination
  • Female
  • Glucose / therapeutic use*
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Insulin / therapeutic use*
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Myocardial Infarction / drug therapy*
  • Potassium / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Research Design

Substances

  • Heparin, Low-Molecular-Weight
  • Insulin
  • Glucose
  • Potassium