Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— IONM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00191282
• Other study ID #: 5509
• Secondary ID: F3Z-MC-IONM
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2005
• Last updated: January 18, 2011
• Start date: October 2002
• Est. completion date: October 2007

Study information

• Verified date: January 2011
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1116
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Diabetes Mellitus, Type 2
• Hyperglycemia
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Insulin lispro
Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study
• 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%
• Insulin glargine
Insulin glargine injected subcutaneous (SC) once daily in the evening until patient completes study.
• Human insulin isophane suspension
Patient adjusted dose, twice daily, injected subcutaneous (SC) before morning and evening meals until patient completes study.
• 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%.

Locations

Country	Name	City	State
Canada	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Toronto	Ontario
Croatia	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Zagreb
Czech Republic	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Praha
Germany	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Dresden
Hungary	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Budapest
India	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	New Delhi
Israel	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Jerusalem
Lebanon	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Beirut
Poland	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Warsaw
Romania	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Brasov
Russian Federation	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Saint Petersburg
Slovakia	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Nitra
Slovenia	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Maribor
South Africa	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Parktown
Spain	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Barcelona
Turkey	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Istanbul
United Kingdom	For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician	Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Canada,  Croatia,  Czech Republic,  Germany,  Hungary,  India,  Israel,  Lebanon,  Poland,  Romania,  Russian Federation,  Slovakia,  Slovenia,  South Africa,  Spain,  Turkey,  United Kingdom, 

References & Publications (3)

Milicevic Z, Raz I, Beattie SD, Campaigne BN, Sarwat S, Gromniak E, Kowalska I, Galic E, Tan M, Hanefeld M. Natural history of cardiovascular disease in patients with diabetes: role of hyperglycemia. Diabetes Care. 2008 Feb;31 Suppl 2:S155-60. doi: 10.233 — View Citation

Milicevic Z, Raz I, Strojek K, Skrha J, Tan MH, Wyatt JW, Beattie SD, Robbins DC; HEART2D Study. Hyperglycemia and its effect after acute myocardial infarction on cardiovascular outcomes in patients with Type 2 diabetes mellitus (HEART2D) Study design. J — View Citation

Raz I, Wilson PW, Strojek K, Kowalska I, Bozikov V, Gitt AK, Jermendy G, Campaigne BN, Kerr L, Milicevic Z, Jacober SJ. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care. 2009 Mar;3 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes

External Links

•   Lilly Clinical Trial Registry