Efficacy Study of Glucagonlike Peptide-1 to Treat Reperfusion Injury

Acute Myocardial Infarction Clinical Trial

Official title:

Protective Effect of Glucagonlike Peptide-1 on Reperfusion Injury in Patients With Acute Myocardial Infarction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02001363
• Other study ID #: S2013-099-01
• Secondary ID: ChinaPLAGH
• Status: Recruiting
• Phase: N/A
• First received: November 27, 2013
• Last updated: February 4, 2016
• Start date: November 2013
• Est. completion date: March 2016

Study information

• Verified date: February 2016
• Source: Chinese PLA General Hospital
• Contact: Wei Ren Chen, M.D.
• Phone: +8610-66939709
• Email: chen_weiren[@]sina.com
• Is FDA regulated: No
• Health authority: China: State Administration of Traditional Chinese Medicine of the People's Republic of ChinaChina: Ethics CommitteeUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction
• Reperfusion Injury

Intervention

Drug:
• liraglutide (Novo Nordisk, Bagsværd, Denmark)
once-daily subcutaneous liraglutide 0.6 mg for 2 days, then gradually increase the dosage, once-daily subcutaneous liraglutide 1.2 mg for 2 days ,once-daily subcutaneous liraglutide 1.8 mg for 3 days
• liraglutide placebo (Novo Nordisk)
once-daily subcutaneous liraglutide placebo 0.6 mg for 2 days, then gradually increase the dosage, once-daily subcutaneous liraglutide placebo 1.2 mg for 2 days ,once-daily subcutaneous liraglutide placebo 1.8 mg for 3 days

Locations

Country	Name	City	State
China	PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chen Wei Ren, MD

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View 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. — View Citation

Lønborg J, Vejlstrup N, Kelbæk H, Bøtker HE, Kim WY, Mathiasen AB, Jørgensen E, Helqvist S, Saunamäki K, Clemmensen P, Holmvang L, Thuesen L, Krusell LR, Jensen JS, Køber L, Treiman M, Holst JJ, Engstrøm 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. — View 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. 200 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the salvage index measured by cardiac magnetic resonance	The primary endpoint was the salvage index measured by cardiac magnetic resonance after 3 months.	3 months after primary percutaneous coronary intervention	No
Secondary	major adverse cardiovascular events (MACE) after 3 months	major adverse cardiovascular events (MACE) after 3 months: recurrent myocardial infarction, recurrent angina, revascularization, heart failure, cardiac death.; treatment-emergent adverse events (TEAEs): hypoglycemia, nausea, acute pancreatitis	3 months after Primary percutaneous coronary intervention	Yes
Secondary	final infarct size after 3 months		3 months after Primary percutaneous coronary intervention	No
Secondary	the levels of high-sensitivity C-reactive protein (hsCRP)		3 months after Primary percutaneous coronary intervention	No
Secondary	nitric oxide (NO) levels		3 months after Primary percutaneous coronary intervention	No