Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Diabetes Mellitus, Type 2, Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Insulin lispro
* Drug: Human insulin isophane suspension (NPH)
* Drug: Insulin glargine
* Drug: Human insulin isophane suspension
* Drug: Human insulin 30/70


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Postprandial: Premeal insulin lispro +/- bedtime NPH | Drug: Insulin lispro<br>* Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study<br>* Other names: Humalog;Drug: Human insulin isophane suspension (NPH)<br>* 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%<br>|
| Active Comparator: 2<br>Fasting: NPH/insulin glargine or human insulin 30/70 | Drug: Insulin glargine<br>* Insulin glargine injected subcutaneous (SC) once daily in the evening until patient completes study.<br>Drug: Human insulin isophane suspension<br>* Patient adjusted dose, twice daily, injected subcutaneous (SC) before morning and evening meals until patient completes study.<br>Drug: Human insulin 30/70<br>* 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%.<br>* Other names: Human insulin 70/30 (in the United States);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced a Primary Combined Outcome | The combined study outcomes consisted of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for acute coronary syndromes (HACS), and coronary revascularization procedures planned after randomization. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Death From Any Cause or Any One of the Primary Outcomes | Primary outcomes in this study consisted of: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for acute coronary syndromes (HACS), and coronary revascularization procedure planned after randomization. | 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) | 
| Number of Participants Who Experienced Any One of the Primary Outcomes Adjusted for Indicators of Metabolic Control | Indicators of metabolic control included glycosylated hemoglobin (HbA1c) and fasting blood glucose concentrations. | Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Primary Outcomes Adjusted for Metabolic Control and Major Cardiovascular (CV) Risk Factors | Primary outcomes adjusted for major cardiovascular (CV) risk factors (blood pressure, cholesterol [total, high density lipoprotein (HDL), and low density lipoprotein (LDL)], triglycerides, smoking, albuminuria, age, gender, and body mass index (BMI). | Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Death From Any Cause |  | Randomization (Day 0) until death from any cause (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Cardiovascular (CV) Death |  | Randomization (Day 0) until cardiovascular death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Myocardial Infarction (MI) | Occurrence of myocardial infarction (MI) (fatal, nonfatal, any). | Randomization (Day 0) until myocardial infarction (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Stroke | Occurrence of stroke (fatal, nonfatal, any). | Randomization (Day 0) until stroke (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Hospitalization for Acute Coronary Syndromes (HACS) |  | Randomization (Day 0) until HACS (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Coronary Revascularization Procedures | Occurrence of all coronary revascularization procedures (angioplasty or coronary artery by-pass surgery) planned after randomization. | Randomization (Day 0) until coronary revascularization procedures (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Amputation for Peripheral Vascular Disease Planned After Randomization |  | Randomization (Day 0) until amputation (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Congestive Heart Failure | Occurrence of congestive heart failure (newly diagnosed after Visit 2). | Randomization (Day 0) until congestive heart failure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Revascularization Procedure for Peripheral Vascular Disease Planned After Randomization |  | Randomization (Day 0) until revascularization procedure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants Who Experienced Coronary Angiography Planned After Randomization |  | Randomization (Day 0) until coronary angiography (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | 
| Number of Participants With Self-Reported Hypoglycemia During Month 1 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 3 (Month 1) | 
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 3 (Month 1) | 
| Number of Participants With Self-Reported Hypoglycemia During Month 3 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 4 (Month 3) | 
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 4 (Month 3) | 
| Number of Participants With Self-Reported Hypoglycemia During Month 6 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 5 (Month 6) | 
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 5 (Month 6) | 
| Number of Participants With Self-Reported Hypoglycemia During Month 9 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 6 (Month 9) | 
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 6 (Month 9) | 
| Number of Participants With Self-Reported Hypoglycemia During Month 12 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 7 (Month 12) | 
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 7 (Month 12) | 
| Number of Participants With Self-Reported Hypoglycemia During Month 18 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 8 (Month 18) | 
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18 | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). | Visit 8 (Month 18) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, MI, heart attack