Clinical trial NCT00191282: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Acute Myocardial Infarction
Keywords: diabetes
MI
heart attack
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2005-09-19
Enrollment: 1116
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants Who Experienced a Primary Combined Outcome
timeFrame: 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 outcomes:
measure: Number of Participants Who Experienced Death From Any Cause or Any One of the Primary Outcomes
timeFrame: 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)
measure: Number of Participants Who Experienced Any One of the Primary Outcomes Adjusted for Indicators of Metabolic Control
timeFrame: Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Primary Outcomes Adjusted for Metabolic Control and Major Cardiovascular (CV) Risk Factors
timeFrame: Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Death From Any Cause
timeFrame: Randomization (Day 0) until death from any cause (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Cardiovascular (CV) Death
timeFrame: Randomization (Day 0) until cardiovascular death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Myocardial Infarction (MI)
timeFrame: Randomization (Day 0) until myocardial infarction (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Stroke
timeFrame: Randomization (Day 0) until stroke (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Hospitalization for Acute Coronary Syndromes (HACS)
timeFrame: Randomization (Day 0) until HACS (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Coronary Revascularization Procedures
timeFrame: Randomization (Day 0) until coronary revascularization procedures (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Amputation for Peripheral Vascular Disease Planned After Randomization
timeFrame: Randomization (Day 0) until amputation (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Congestive Heart Failure
timeFrame: Randomization (Day 0) until congestive heart failure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Revascularization Procedure for Peripheral Vascular Disease Planned After Randomization
timeFrame: Randomization (Day 0) until revascularization procedure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants Who Experienced Coronary Angiography Planned After Randomization
timeFrame: Randomization (Day 0) until coronary angiography (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
measure: Number of Participants With Self-Reported Hypoglycemia During Month 1
timeFrame: Visit 3 (Month 1)
measure: Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1
timeFrame: Visit 3 (Month 1)
measure: Number of Participants With Self-Reported Hypoglycemia During Month 3
timeFrame: Visit 4 (Month 3)
measure: Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3
timeFrame: Visit 4 (Month 3)
measure: Number of Participants With Self-Reported Hypoglycemia During Month 6
timeFrame: Visit 5 (Month 6)
measure: Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6
timeFrame: Visit 5 (Month 6)
measure: Number of Participants With Self-Reported Hypoglycemia During Month 9
timeFrame: Visit 6 (Month 9)
measure: Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9
timeFrame: Visit 6 (Month 9)
measure: Number of Participants With Self-Reported Hypoglycemia During Month 12
timeFrame: Visit 7 (Month 12)
measure: Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12
timeFrame: Visit 7 (Month 12)
measure: Number of Participants With Self-Reported Hypoglycemia During Month 18
timeFrame: Visit 8 (Month 18)
measure: Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18
timeFrame: Visit 8 (Month 18)
Other outcomes:
measure: Summary of Reasons for Deaths
timeFrame: Randomization (Day 0) to death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Locations:
city: Toronto
country: Canada
facility: 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
state: Ontario
city: Zagreb
country: Croatia
facility: 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
city: Praha
country: Czech Republic
facility: 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
city: Dresden
country: Germany
facility: 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
city: Budapest
country: Hungary
facility: 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
city: New Delhi
country: India
facility: 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
city: Jerusalem
country: Israel
facility: 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
city: Beirut
country: Lebanon
facility: 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
city: Warsaw
country: Poland
facility: 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
city: Brasov
country: Romania
facility: 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
city: Saint Petersburg
country: Russian Federation
facility: 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
city: Nitra
country: Slovakia
facility: 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
city: Maribor
country: Slovenia
facility: 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
city: Parktown
country: South Africa
facility: 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
city: Barcelona
country: Spain
facility: 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
city: Istanbul
country: Turkey
facility: 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
city: Liverpool
country: United Kingdom
facility: 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
Study officials:
affiliation: Eli Lilly and Company
name: 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
References:
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;32(3):381-6. doi: 10.2337/dc08-1671.
citation: 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.
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 Diabetes Complications. 2005 Mar-Apr;19(2):80-7. doi: 10.1016/j.jdiacomp.2004.06.003.
citation: 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.