title: 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.
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.
authors.affiliation: Department of Medicine, McMaster University, and Population Health Research Institute, Hamilton General Hospital, Hamilton, Canada. yusufs@mcmaster.ca <yusufs@mcmaster.ca>
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Shamir R
authors.initials: SR
authors.lastname: Mehta
authors.forename: Rafael
authors.initials: R
authors.lastname: Díaz
authors.forename: Ernesto
authors.initials: E
authors.lastname: Paolasso
authors.forename: Prem
authors.initials: P
authors.lastname: Pais
authors.forename: Denis
authors.initials: D
authors.lastname: Xavier
authors.forename: Changchun
authors.initials: C
authors.lastname: Xie
authors.forename: Rashid J
authors.initials: RJ
authors.lastname: Ahmed
authors.forename: Khawar
authors.initials: K
authors.lastname: Khazmi
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Lisheng
authors.initials: L
authors.lastname: Liu
mesh_terms: D002985:Clinical Protocols; D004359:Drug Therapy, Combination; D005260:Female; D005947:Glucose / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000188:drug therapy*; D011188:Potassium / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D006495:Heparin, Low-Molecular-Weight; D007328:Insulin; D005947:Glucose; D011188:Potassium