REsearching Coronary REduction by Appropriately Targeting Euglycemia (RECREATE Pilot Study) (RECREATE Pilot)

An International Multicentre Randomized Controlled Trial of Intensive Insulin Therapy Targeting Normoglycemia In Acute Myocardial Infarction: the RECREATE (REsearching Coronary REduction by Appropriately Targeting Euglycemia) Pilot Study

Insulin will safely reduce glucose levels in patients with acute ST-elevation myocardial infarction and admission hyperglycemia.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia; Myocardial Infarction; Cardiovascular Diseases
• Intervention / Treatment: Drug: glulisine insulin, glargine insulin

Detailed Description

Patients will be randomly assigned to either the control arm and will receive usual AMI care or the experimental arm, which will include routine AMI care as well as intensive therapy intervention.

In addition to the capillary blood glucose measurements obtained to titrate insulin doses in the experimental arm patients, laboratory plasma glucose will be drawn in all patients at randomization, 10, 24, 48, and 72 hours post randomization, 7 days post randomization (or hospital discharge if that occurs first), and 30 days post randomization.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Adrogue,, Buenos Aires, Argentina
      • Instituto Médico Adrogué
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences, General Site
• India
  • Nagpur, India, 440012
    • Avanti Institute of Cardiology
  • Assam
    • Dt. Dibrugarh, Assam, India, 786002
      • Assam Medical College Hospital
  • Chattisgarh
    • Raipur, Chattisgarh, India, 492001
      • Lifeworth Super Specialty Hospital
  • Haryana
    • Rohtak, Haryana, India, 124001
      • Post Graduate Institute of Medical
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • St. Johns Medical College
    • Shimoga, Karnataka, India, 577201
      • Nanjappa Hospital
  • Kerala
    • Calicut, Kerala, India, 673004
      • Baby Memorial Hospital
    • Kottayam, Kerala, India, 686016
      • Caritas Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • KEM Hospital
    • Wardha, Maharashtra, India, 442102
      • MGIMS
  • Tamilnadu
    • Chennai, Tamilnadu, India, 600023
      • Railway Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Both nondiabetic patients and patients with non-insulin-requiring type 2 diabetes mellitus admitted with a suspected AMI are eligible if they meet the following criteria:

• Signs or symptoms of AMI with definite ECG changes, defined as persistent ST-segment elevation (> or = than 1 mm)in two or more contiguous leads, or new left bundle branch block
• Onset of symptoms within 24 hours before hospital presentation
• Capillary blood glucose level on presentation > or = 8.0 mmol/L (144 mg/dL)

Exclusion Criteria:

• Patient with conditions that REQUIRE the administration of insulin, including:

  • Type 1 diabetes mellitus, defined by a documented history of diabetes mellitus before the age of 30
  • Type 2 diabetes mellitus that was treated with insulin prior to AMI presentation
  • Type 2 diabetes mellitus that is known to be very poorly controlled (e.g. admission capillary blood glucose > 16.0 mmol/L (288 mg/dL)or marked elevation in glucose for which the site investigator plans to treat with insulin therapy)
• A history of severe hypoglycemic episodes (defined as hypoglycemia with symptoms which the patient is unable to reverse without the assistance of another person) within the past two years
• Known or suspected end-stage liver disease (due to the risk of hypoglycemia in the setting of liver dysfunction and consequent impaired regulation of glucose homeostasis)
• Cardiogenic shock on admission (due to the inaccuracy of glucose meter readings)
• Documented pregnancy
• Any concomitant disease (e.g. cancer) that might limit life expectancy to less than 90 days
• Anticipated poor adherence with study treatments or an other factor that might jeopardize 90-day follow-up (e.g. no fixed address, long distance to hospital, etc.)
• Prior enrollment in this trial or current enrollment in another trial of ST-segment elevation myocardial infarction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Patients assigned to the control arm will receive usual care for AMI, according to local practice of each participating centre.
Experimental: Intervention; The experimental arm will have an IV infusion of glulisine insulin started directly after randomization for at least 24 hours and for as long as CCU-level care is required, and the insulin infusion will be adjusted to achieve and maintain a target glucose range of 5.0-6.6 mmol/L (90-118 mg/dL). Once transferred to the ward, patients in the experimental arm will switch to glargine insulin and will continue this treatment for the remainder of their hospitalization and after hospital discharge, for a total duration of 30 days post randomization.	Drug: glulisine insulin, glargine insulin; IV infusion of glulisine, SC injection of glargine; Other Names: Apidra, Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The 24-hour difference in mean glucose between the two study groups.	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
The difference in mean glucose level achieved at 7 days or hospital discharge (whichever is first)	7 days or discharge
The difference in mean glucose level achieved at 30 days between study groups	30 days
Nonfatal recurrent myocardial infarction, nonfatal stroke, or cardiovascular death (as a composite and as separate outcomes)	Discharge, 30 days, 90 days, 1 year
Rehospitalization for congestive heart failure	Discharge, 30 days, 90 days, 1 year
All cause mortality	Discharge, 30 days, 90 days, 1 year
Resuscitated cardiac arrest or life-threatening arrhythmia (as a composite and as separate outcomes)	Discharge, 30 days, 90 days, 1 year
Cardiogenic shock	Discharge, 30 days, 90 days, 1 year
Cardiac procedures	Discharge, 30 days, 90 days, 1 year
Rehospitalization for any cause	Discharge, 30 days, 90 days, 1 year
Symptomatic and severe hypoglycemic episodes	Discharge, 30 days, 90 days, 1 year
Hypokalemic episodes	Discharge

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Hertzel Gerstein, MD, MSc, FRCPC, McMaster University; Principal Investigator: Salim Yusuf, DPhil, FRCPC, FRSC, McMaster University

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: March 18, 2008
• First Submitted That Met QC Criteria: March 18, 2008
• First Posted (Estimate): March 21, 2008

Study Record Updates

• Last Update Posted (Estimate): June 16, 2010
• Last Update Submitted That Met QC Criteria: June 15, 2010
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Insulin; Clinical Trial
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Myocardial Infarction; Hyperglycemia; Infarction; Cardiovascular Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin Glargine; Insulin glulisine
• Other Study ID Numbers: RECREATE Pilot

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No