Effects of Glucagon Like Peptide-1 on No-reflow

Effects of Glucagon Like Peptide-1 on No-reflow in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

The investigators planned to evaluate the effects of liraglutide on no-reflow in patients with acute ST-segment elevation myocardial infarction (STEMI).

Study Overview

• Status: Unknown
• Conditions: Acute ST-segment Elevation Myocardial Infarction
• Intervention / Treatment: Drug: liraglutide; Drug: placebo

Detailed Description

Acute myocardial infarction (AMI) is a major cause of mortality and morbidity. Primary percutaneous coronary intervention (PCI) is currently the most effective treatment strategy for AMI. Brisk thrombolysis in myocardial infarction (TIMI) grade 3 flow immediately after PCI in patients with AMI is associated with improved clinical outcomes compared with lower flow grades. However, myocardial reperfusion is suboptimal in many patients, mostly because of the 'no-reflow' phenomenon. No-reflow is defined as suboptimal myocardial reperfusion in part of the coronary circulation without angiographic evidence of mechanical vessel obstruction. To date, however, very few drugs have been shown to reverse established no-reflow.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates plasma glucose, and GLP-1 analogues were recently introduced for the treatment of acute myocardial infarction. GLP-1 has antioxidant and anti-inflammatory properties, and may protect endothelial function. Experimental studies have also revealed that GLP-1 or its analogues protect against reperfusion injury in pigs. Exenatide, a GLP-1 analogue, was reported to reduce reperfusion injury in patients with ST-segment elevation myocardial infarction. Similarly, liraglutide was reported to reduce cardiac rupture and infarct size and improve cardiac output in normal and diabetic mice. To date, however, there is no clinical evidence for the effects of liraglutide on no-reflow in patients with AMI. Therefore, the aim of this study was to evaluate the effects of liraglutide pretreatment on myocardial no-reflow of prime PCI in patients with AMI.

• Study Type: Interventional
• Enrollment (Anticipated): 190
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: wei ren chen, M.D.; Phone Number: +8601066876221; Email: chen_weiren@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with ST-segment elevation myocardial infarction were eligible for the study.

Exclusion Criteria:

Patients were excluded for the following reasons: unconscious at presentation; had cardiogenic shock, hypoglycaemia, or diabetic ketoacidosis; had a history of myocardial infarction, stent thrombosis, or renal insufficiency; or had previously undergone coronary artery bypass surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLP-1 group; The treatment started 30 min before PCI with a dose of 1.8 mg liraglutide (the treatment was administered in the ambulance).	Drug: liraglutide; Liraglutide were taken 30 min before PCI.; Other Names: glucagon like peptide-1
Placebo Comparator: Control group; the treatment started 30 min before PCI with a dose of 1.8 mg placebo (the treatment was administered in the ambulance).	Drug: placebo; Placebo were taken 30 min before PCI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
a change in the prevalence of no-reflow	The primary efficacy variable was the prevalence of no-reflow assessed immediately post procedure.	immediately after PCI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
a change in troponin T	Secondary efficacy variable was troponin T level.	immediately after PCI, at 1,3,5 days after PCI
a change in high-sensitivity C-reactive protein (hsCRP)	Secondary efficacy variable was high-sensitivity C-reactive protein level.	immediately after PCI, at 1,3,5 days after PCI
a change in superoxide dismutase (SOD)	Secondary efficacy variable was superoxide dismutase level.	immediately after PCI, at 1,3,5 days after PCI

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
differences in the incidences of treatment-emergent adverse events	Treatment-emergent adverse events (TEAEs): hypoglycaemia, pancreatitis, thyroid cancer	immediately after PCI, at 1,3,5 days after PCI

Collaborators and Investigators

• Sponsor: Chen Wei Ren, MD

Publications and helpful links

General Publications

• Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003 Jan 4;361(9351):13-20. doi: 10.1016/S0140-6736(03)12113-7.
• Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, Verlaan CW, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G, Hoefer IE. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009 Feb 10;53(6):501-10. doi: 10.1016/j.jacc.2008.10.033.
• Gibson CM, Cannon CP, Murphy SA, Marble SJ, Barron HV, Braunwald E; TIMI Study Group. Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation. 2002 Apr 23;105(16):1909-13. doi: 10.1161/01.cir.0000014683.52177.b5.
• Rezkalla SH, Kloner RA. Coronary no-reflow phenomenon: from the experimental laboratory to the cardiac catheterization laboratory. Catheter Cardiovasc Interv. 2008 Dec 1;72(7):950-7. doi: 10.1002/ccd.21715.
• Muller O, Trana C, Eeckhout E. Myocardial no-reflow treatment. Curr Vasc Pharmacol. 2013 Mar 1;11(2):278-85.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Hypoglycemic Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: 301xnk