Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes

Official Title: “Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes (HEART2D)”

The primary objective was to demonstrate a difference between two insulin strategies, one targeting postprandial (PP) hyperglycemia and the other targeting fasting and interprandial hyperglycemia, on time until the first combined adjudicated cardiovascular (CV) event (primary outcome defined as CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or hospitalized acute coronary syndrome).

The purpose of this study is to evaluate the effect of two different treatment strategies on CV outcomes in patients with type 2 diabetes while aiming to achieve and maintain HbA1c <7.0% in both groups. Only patients who have recently experienced an acute MI will be considered for participation in this trial.

Intervention(s) in this Clinical Trial

• Drug: Insulin lispro
  • Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study
• Drug: Human insulin isophane suspension (NPH)
  • Patient adjusted dose, daily at bedtime, injected subcutaneous (SC) until patient completes study. To be added to the arm only if patient has two consecutive HbA1c values >8.0%
• Drug: Insulin glargine
  • Insulin glargine injected subcutaneous (SC) once daily in the evening until patient completes study.
• Drug: Human insulin isophane suspension
  • Patient adjusted dose, twice daily, injected subcutaneous (SC) before morning and evening meals until patient completes study.
• Drug: Human insulin 30/70
  • Patient adjusted dose, twice daily before the morning and evening meals, injected subcutaneous (SC) until patient completes study. To replace insulin regimen in this arm only if patient has two consecutive HbA1c values >8.0%.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Postprandial: Premeal insulin lispro +/- bedtime NPH
• Active Comparator: 2
  • Fasting: NPH/insulin glargine or human insulin 30/70

Primary Measures

• Number of Participants Who Experienced a Primary Combined Outcome
  • Time Frame: Randomization (Day 0) until first occurrence of primary combined outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes

Secondary Measures

• Number of Participants Who Experienced Death From Any Cause or Any One of the Primary Outcomes
  • Time Frame: Randomization (Day 0) until death from any cause or one of the primary outcomes (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Any One of the Primary Outcomes Adjusted for Indicators of Metabolic Control
  • Time Frame: Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Primary Outcomes Adjusted for Metabolic Control and Major Cardiovascular (CV) Risk Factors
  • Time Frame: Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Death From Any Cause
  • Time Frame: Randomization (Day 0) until death from any cause (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Cardiovascular (CV) Death
  • Time Frame: Randomization (Day 0) until cardiovascular death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Myocardial Infarction (MI)
  • Time Frame: Randomization (Day 0) until myocardial infarction (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Stroke
  • Time Frame: Randomization (Day 0) until stroke (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Hospitalization for Acute Coronary Syndromes (HACS)
  • Time Frame: Randomization (Day 0) until HACS (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Coronary Revascularization Procedures
  • Time Frame: Randomization (Day 0) until coronary revascularization procedures (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Amputation for Peripheral Vascular Disease Planned After Randomization
  • Time Frame: Randomization (Day 0) until amputation (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Congestive Heart Failure
  • Time Frame: Randomization (Day 0) until congestive heart failure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Revascularization Procedure for Peripheral Vascular Disease Planned After Randomization
  • Time Frame: Randomization (Day 0) until revascularization procedure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants Who Experienced Coronary Angiography Planned After Randomization
  • Time Frame: Randomization (Day 0) until coronary angiography (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
    Safety Issue?: Yes
• Number of Participants With Self-Reported Hypoglycemia During Month 1
  • Time Frame: Visit 3 (Month 1)
    Safety Issue?: Yes
• Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1
  • Time Frame: Visit 3 (Month 1)
    Safety Issue?: Yes
• Number of Participants With Self-Reported Hypoglycemia During Month 3
  • Time Frame: Visit 4 (Month 3)
    Safety Issue?: Yes
• Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3
  • Time Frame: Visit 4 (Month 3)
    Safety Issue?: Yes
• Number of Participants With Self-Reported Hypoglycemia During Month 6
  • Time Frame: Visit 5 (Month 6)
    Safety Issue?: Yes
• Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6
  • Time Frame: Visit 5 (Month 6)
    Safety Issue?: Yes
• Number of Participants With Self-Reported Hypoglycemia During Month 9
  • Time Frame: Visit 6 (Month 9)
    Safety Issue?: Yes
• Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9
  • Time Frame: Visit 6 (Month 9)
    Safety Issue?: Yes
• Number of Participants With Self-Reported Hypoglycemia During Month 12
  • Time Frame: Visit 7 (Month 12)
    Safety Issue?: Yes
• Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12
  • Time Frame: Visit 7 (Month 12)
    Safety Issue?: Yes
• Number of Participants With Self-Reported Hypoglycemia During Month 18
  • Time Frame: Visit 8 (Month 18)
    Safety Issue?: Yes
• Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18
  • Time Frame: Visit 8 (Month 18)
    Safety Issue?: Yes

Inclusion Criteria:

• Are at least 30 years old
• Have had type 2 diabetes for at least 3 months prior to Visit 1
• Were admitted to the Coronary Care Unit (CCU) within 18 days prior to Visit 1 for an acute MI
• Are capable and willing to do specified study procedures
• Have given informed consent to participate in the study in accordance with local regulations

Exclusion Criteria:

• Were on one of the following therapies prior to admission to the CCU for the recent
• MI: a)diet therapy only and have glycosylated hemoglobin (HbA1c) <1.15 times the upper limit of normal or b) an intensive basal/bolus insulin regimen
• Are using any oral antihyperglycemic medication at the time of Visit 2 and are unwilling to stop the use of such medication for the duration of the study
• Have substantial myocardial damage, which would significantly outweigh the potential benefit of the treatment strategies for diabetes
• Have the most severe form of congestive heart failure
• Have liver disease so severe that it precludes the patient from following and completing the protocol

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eli Lilly and Company Industry

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9am-5pm Eastern time (UTC/GMT - 5 hours, EST) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00191282

Study ID Number: 5509

ClinicalTrials.gov Identifier: NCT00191282

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry