Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes (IONM)

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00191282
First received: September 12, 2005
Last updated: January 18, 2011
Last verified: January 2011
  Purpose

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).


Condition Intervention Phase
Diabetes Mellitus, Type 2
Acute Myocardial Infarction
Drug: Insulin lispro
Drug: Human insulin isophane suspension (NPH)
Drug: Insulin glargine
Drug: Human insulin isophane suspension
Drug: Human insulin 30/70
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes (HEART2D)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome 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) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome 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) ] [ Designated as safety issue: Yes ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    Indicators of metabolic control included glycosylated hemoglobin (HbA1c) and fasting blood glucose concentrations.

  • 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) ] [ Designated as safety issue: Yes ]
    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).

  • 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) ] [ Designated as 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) ] [ Designated as 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) ] [ Designated as safety issue: Yes ]
    Occurrence of myocardial infarction (MI) (fatal, nonfatal, any).

  • 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) ] [ Designated as safety issue: Yes ]
    Occurrence of stroke (fatal, nonfatal, any).

  • 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) ] [ Designated as 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) ] [ Designated as safety issue: Yes ]
    Occurrence of all coronary revascularization procedures (angioplasty or coronary artery by-pass surgery) planned after randomization.

  • 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) ] [ Designated as 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) ] [ Designated as safety issue: Yes ]
    Occurrence of congestive heart failure (newly diagnosed after Visit 2).

  • 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) ] [ Designated as 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) ] [ Designated as safety issue: Yes ]
  • Number of Participants With Self-Reported Hypoglycemia During Month 1 [ Time Frame: Visit 3 (Month 1) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1 [ Time Frame: Visit 3 (Month 1) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Self-Reported Hypoglycemia During Month 3 [ Time Frame: Visit 4 (Month 3) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3 [ Time Frame: Visit 4 (Month 3) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Self-Reported Hypoglycemia During Month 6 [ Time Frame: Visit 5 (Month 6) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6 [ Time Frame: Visit 5 (Month 6) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Self-Reported Hypoglycemia During Month 9 [ Time Frame: Visit 6 (Month 9) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9 [ Time Frame: Visit 6 (Month 9) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Self-Reported Hypoglycemia During Month 12 [ Time Frame: Visit 7 (Month 12) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12 [ Time Frame: Visit 7 (Month 12) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Self-Reported Hypoglycemia During Month 18 [ Time Frame: Visit 8 (Month 18) ] [ Designated as safety issue: Yes ]
    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).

  • Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18 [ Time Frame: Visit 8 (Month 18) ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 1116
Study Start Date: October 2002
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Postprandial: Premeal insulin lispro +/- bedtime NPH
Drug: Insulin lispro
Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study
Other Name: Humalog
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%
Active Comparator: 2
Fasting: NPH/insulin glargine or human insulin 30/70
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%.
Other Name: Human insulin 70/30 (in the United States)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00191282

  Show 17 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9am-5pm Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00191282     History of Changes
Other Study ID Numbers: 5509, F3Z-MC-IONM
Study First Received: September 12, 2005
Results First Received: October 17, 2008
Last Updated: January 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
diabetes
MI
heart attack

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperglycemia
Infarction
Myocardial Infarction
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Insulin LISPRO
Glargine
Insulin
Insulin, NPH
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014