Clinical trial NCT02001363: Efficacy Study of Glucagonlike Peptide-1 to Treat Reperfusion Injury
Official title: Protective Effect of Glucagonlike Peptide-1 on Reperfusion Injury in Patients With Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Myocardial Infarction
Keywords: Reperfusion injury
Liraglutide
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2013-12-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators planned to research the cardioprotective effects of intravenous liraglutide on reperfusion injury.

Detailed description: Acute myocardial infarction is a major cause of mortality and morbidity. Primary percutaneous coronary intervention (pPCI) is currently the most effective treatment strategy in acute myocardial infarction. However, a sizable number of patients fail to restore optimal myocardial reperfusion, mostly because of the 'no-reflow' phenomenon. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates plasma glucose, and recently GLP-1 analogues have been introduced for the treatment of type-2 diabetes. In experimental studies, GLP-1 or its analogues protect against reperfusion injury-induced cell death. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Liraglutide(GLP-1) is safe and effective to reduce weight,serum lipid levels and blood pressure. Liraglutide can reduce cardiac rupture (12 of 60 versus 46 of 60; P=0.0001) and infarct size (21±2% versus 29±3%, P=0.02) and improved cardiac output (12.4±0.6 versus 9.7±0.6 ml/min; P=0.002) in normal and diabetic mice. The investigators planned to research the cardioprotective effects of intravenous liraglutide administered prior to reperfusion and continued after restoration of coronary blood flow in patients with STEMI undergoing pPCI.

Eligibility criteria: Inclusion Criteria:

Patients were eligible if they were 18 years or older and presented within 12 h from the onset of symptoms and signs of ST-segment elevation myocardial infarction to the catheterization laboratory.

Exclusion Criteria:

The patients were not considered for enrolment if they presented with unconsciousness, cardiogenic shock, hypoglycaemia, diabetic ketoacidosis, previous myocardial infarction, stent thrombosis, known renal insufficiency, or previous coronary artery bypass operation.

Primary outcomes:
measure: the salvage index measured by cardiac magnetic resonance
timeFrame: 3 months after primary percutaneous coronary intervention
Secondary outcomes:
measure: major adverse cardiovascular events (MACE) after 3 months
timeFrame: 3 months after Primary percutaneous coronary intervention
measure: final infarct size after 3 months
timeFrame: 3 months after Primary percutaneous coronary intervention
measure: the levels of high-sensitivity C-reactive protein (hsCRP)
timeFrame: 3 months after Primary percutaneous coronary intervention
measure: nitric oxide (NO) levels
timeFrame: 3 months after Primary percutaneous coronary intervention
Other outcomes:
Locations:
city: Beijing
country: China
facility: PLA General Hospital
state: Beijing
Study officials:
affiliation: World Health Organization
name: Yun Dai Chen, M.D.
role: STUDY_DIRECTOR
References:
citation: Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B; LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009 Feb 7;373(9662):473-81. doi: 10.1016/S0140-6736(08)61246-5. Epub 2008 Sep 24.
citation: Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, Jorgensen E, Helqvist S, Saunamaki K, Clemmensen P, Holmvang L, Thuesen L, Krusell LR, Jensen JS, Kober L, Treiman M, Holst JJ, Engstrom T. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012 Jun;33(12):1491-9. doi: 10.1093/eurheartj/ehr309. Epub 2011 Sep 14.
citation: Liu H, Dear AE, Knudsen LB, Simpson RW. A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules. J Endocrinol. 2009 Apr;201(1):59-66. doi: 10.1677/JOE-08-0468. Epub 2009 Jan 9.
citation: Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, Baggio LL, Henkelman RM, Husain M, Drucker DJ. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009 Apr;58(4):975-83. doi: 10.2337/db08-1193. Epub 2009 Jan 16.
citation: Huang M, Wei R, Wang Y, Su T, Li Q, Yang X, Chen X. Protective effect of glucagon-like peptide-1 agents on reperfusion injury for acute myocardial infarction: a meta-analysis of randomized controlled trials. Ann Med. 2017 Nov;49(7):552-561. doi: 10.1080/07853890.2017.1306653. Epub 2017 Mar 31.
citation: Chen WR, Chen YD, Tian F, Yang N, Cheng LQ, Hu SY, Wang J, Yang JJ, Wang SF, Gu XF. Effects of Liraglutide on Reperfusion Injury in Patients With ST-Segment-Elevation Myocardial Infarction. Circ Cardiovasc Imaging. 2016 Dec;9(12):e005146. doi: 10.1161/CIRCIMAGING.116.005146.