Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes

NCT ID: NCT00191282

Last Updated: 2011-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-10-31
• Study Completion Date: 2007-10-31

Brief 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).

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.

Conditions

Diabetes Mellitus, Type 2; Acute Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Postprandial: Premeal insulin lispro +/- bedtime NPH

Group Type: EXPERIMENTAL

Insulin lispro

Intervention Type: DRUG

Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study

Human insulin isophane suspension (NPH)

Intervention Type: DRUG

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%

2

Fasting: NPH/insulin glargine or human insulin 30/70

Group Type: ACTIVE_COMPARATOR

Insulin glargine

Intervention Type: DRUG

Insulin glargine injected subcutaneous (SC) once daily in the evening until patient completes study.

Human insulin isophane suspension

Intervention Type: DRUG

Patient adjusted dose, twice daily, injected subcutaneous (SC) before morning and evening meals until patient completes study.

Human insulin 30/70

Intervention Type: DRUG

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%.

Interventions

Insulin lispro

Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study

Intervention Type: 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%

Intervention Type: DRUG

Insulin glargine

Insulin glargine injected subcutaneous (SC) once daily in the evening until patient completes study.

Intervention Type: DRUG

Human insulin isophane suspension

Patient adjusted dose, twice daily, injected subcutaneous (SC) before morning and evening meals until patient completes study.

Intervention Type: 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%.

Intervention Type: DRUG

Other Intervention Names

Humalog; Human insulin 70/30 (in the United States)

Eligibility 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

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Eli Lilly

Principal Investigators

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

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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, 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

Zagreb, , 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

Prague, , Czechia

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, , 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

Budapest, , 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

New Delhi, , 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

Jerusalem, , 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

Beirut, , 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

Warsaw, , 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

Brasov, , 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

Saint Petersburg, , Russia

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, , 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

Maribor, , 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

Parktown, , 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

Barcelona, , 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

Istanbul, , Turkey (Türkiye)

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, , United Kingdom

Countries

Canada; Croatia; Czechia; Germany; Hungary; India; Israel; Lebanon; Poland; Romania; Russia; Slovakia; Slovenia; South Africa; Spain; Turkey (Türkiye); United Kingdom

References

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;32(3):381-6. doi: 10.2337/dc08-1671.

Reference Type: RESULT

PMID: 19246588 (View on PubMed)

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: 10.2337/dc08-s240.

Reference Type: RESULT

PMID: 18227478 (View on PubMed)

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 Diabetes Complications. 2005 Mar-Apr;19(2):80-7. doi: 10.1016/j.jdiacomp.2004.06.003.

Reference Type: RESULT

PMID: 15745837 (View on PubMed)

Raz I, Ceriello A, Wilson PW, Battioui C, Su EW, Kerr L, Jones CA, Milicevic Z, Jacober SJ. Post hoc subgroup analysis of the HEART2D trial demonstrates lower cardiovascular risk in older patients targeting postprandial versus fasting/premeal glycemia. Diabetes Care. 2011 Jul;34(7):1511-3. doi: 10.2337/dc10-2375. Epub 2011 May 18.

Reference Type: DERIVED

PMID: 21593301 (View on PubMed)

Other Identifiers

F3Z-MC-IONM

Identifier Type: OTHER

Identifier Source: secondary_id

5509

Identifier Type: -

Identifier Source: org_study_id