GLP-1 Receptor Agonist for Reduction of Myocardial Injury After Non-cardiac Surgery

NCT ID: NCT06324461

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 372 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-20
• Study Completion Date: 2028-12-31

Brief Summary

This is an investigator initiated, multi-center, open-labelled, superiority randomized controlled trial of 372 patients undergoing elective non-cardiac surgery. Recruited patients will be randomized in a 2:1 ratio to receive single subcutaneous dose of Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RAs) 1 to 14 days prior to surgery or receive routine care.

Dulaglutide (Trulicity; Eli Lilly, USA) is chosen as GLP-1 Receptor Agonists investigational drug for this study. Apart from peri-operative routine care, all recruited subjects will undergo physical, respiratory and cardiac assessments including electrocardiography and blood check including cardiac enzymes. Myocardial injury, cardiovascular outcomes and safety will be assessed and evaluated for efficacy and safety of this prophylactic measurement for the reduction of myocardial injury after non-cardiac surgery.

Detailed Description

Myocardial injury following non-cardiac surgery (MINS) is increasingly recognized as a major cause of peri-operative morbidity and mortality worldwide. MINS is defined as post-operative cardiomyocyte injury that can be detected by high-sensitive troponin assays, which may or may not be associated with symptoms or changes on electrocardiogram (ECG). Globally, it was found that 35.5% patients had MINS with elevated troponin level in the early post-operative period. Post-operative troponin T level strongly correlated with peri-operative mortality. It was demonstrated that elevated troponin T level to 14-20 ng/L after surgery significantly increased 30-day mortality with hazard ratio of 9.11. As the global volume of non-cardiac surgeries continues to increase, there is an urgent need to identify effective strategies to minimize MINS. To date, no pharmacological intervention has been shown to safely reduce MINS.

This study will evaluate the effect of pre-operative glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on MINS. GLP-1 is a peptide hormone produced by intestinal epithelial endocrine L-cells that stimulates insulin secretion and inhibits glucagon secretion. GLP-1 RAs have been used to treat both diabetic and non-diabetic conditions. In landmark cardiovascular outcome trials, GLP-1 RAs were shown to reduce major adverse cardiovascular events (MACE) when compared with placebo. GLP-A RAs exert beneficial effects by stabilizing atherosclerotic plaques. Animal studies revealed that a GLP-1 RAs attenuate activation and recruitment of monocytes and macrophages to the arterial wall by suppressing expression of interleukin 6 (IL-6), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule 1 (VCAM-1), and E- selectin (SELE). GLP-1 RAs also suppress vascular smooth muscle cell proliferation and migration via the Cyclic adenosine monophosphate (cAMP) or protein kinase A (PKA) pathway. Another key advantage of using GLP-1 RA in the context of surgery is intra-operative stabilization of glycemic level. It is well established that intra-operative hyperglycemia is associated with increased risk of MINS. Prospective studies have revealed that GLP-1 RA infusion during the peri-operative period resulted in better glycemic control among diabetic and non-diabetic patients without significantly increasing hypoglycemia risk.

The "Glucagon-like Peptide-1 Receptor Agonist for Reduction of Myocardial Injury after Non-Cardiac Surgery" (GLUMINS) trial is an investigator initiated, multi-center, open-labelled Randomized Controlled Trial that will determine the effect of pre-operative GLP-1 RAs on MINS. The study hypothesis is that pre-operative GLP-1 RAs will reduce myocardial injury in patients undergoing non-cardiac surgery. Critically needed new knowledge will be generated about the effectiveness of GLP-1 RAs as a peri-operative intervention to reduce MINS, which may fundamentally alter peri-operative management in non-cardiac surgeries.

Conditions

Myocardial Injury

Study Design

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

Study Groups

Dulaglutide group

Subject randomized into this group will receive single subcutaneous dose of Dulaglutide 0.75mg 1 to 14 days prior to surgery, on top of routine peri-operative care

Group Type: EXPERIMENTAL

Dulaglutide 0.75mg subcutaneous injection

Intervention Type: DRUG

Subject randomized into treatment group will receive single subcutaneous dose of Dulaglutide 0.75mg 1 to 14 days prior to surgery

Control group

Subject randomized into this group will receive routine peri-operative care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dulaglutide 0.75mg subcutaneous injection

Subject randomized into treatment group will receive single subcutaneous dose of Dulaglutide 0.75mg 1 to 14 days prior to surgery

Intervention Type: DRUG

Other Intervention Names

Trulicity 0.75mg subcutaneous injection

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Planned elective intermediate to high risk non-cardiac surgery under general anesthesia
• Anticipated to remain hospitalized for at least one night after surgery
• Voluntarily agrees to participate by providing written informed consent

Exclusion Criteria

• History of symptomatic hypoglycemia within 1 month of recruitment
• History of pancreatitis
• Diabetic retinopathy
• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Acute coronary syndrome, decompensated heart failure, cardiogenic shock, or myocarditis within 1 month of recruitment
• Stroke or transient ischemic attack within 1 month of recruitment
• Known severe liver disease (Child-Pugh B or C)
• Stage 5 chronic kidney disease (estimated glomerular filtration rate (eGFR) by Modified Diet in Renal Disease (MDRD) equation < 15 mL/min)
• Recent use of GLP-1 RA within 1 month of recruitment
• Known allergy or hypersensitivity to GLP-1 RA
• Women of childbearing age who are not taking effective contraception, or who are pregnant or breast-feeding
• Use of Dipeptidyl peptidase-4 inhibitor(DPP4i)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Research Grants Council, Hong Kong

OTHER

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Wong Chun Ka

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chun Ka Wong, Clinical Assistant Professor

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

Duchess of Kent Children's Hospital at Sandy Bay

Hong Kong, Hong Kong SAR, China

Site Status: NOT_YET_RECRUITING

Queen Mary Hospital

Hong Kong, Hong Kong SAR, China

Site Status: RECRUITING

Tung Wah Hospital

Hong Kong, Hong Kong SAR, China

Site Status: RECRUITING

Countries

China

Central Contacts

Chun Ka Wong, Clinical Assistant Professor

Role: CONTACT

wongeck@hku.hk

+852 2255 3597

Lily Hung, Bachelor

Role: CONTACT

nga98@hku.hk

+852 2255 4169

References

Writing Committee for the VSI, Devereaux PJ, Biccard BM, Sigamani A, Xavier D, Chan MTV, Srinathan SK, Walsh M, Abraham V, Pearse R, Wang CY, Sessler DI, Kurz A, Szczeklik W, Berwanger O, Villar JC, Malaga G, Garg AX, Chow CK, Ackland G, Patel A, Borges FK, Belley-Cote EP, Duceppe E, Spence J, Tandon V, Williams C, Sapsford RJ, Polanczyk CA, Tiboni M, Alonso-Coello P, Faruqui A, Heels-Ansdell D, Lamy A, Whitlock R, LeManach Y, Roshanov PS, McGillion M, Kavsak P, McQueen MJ, Thabane L, Rodseth RN, Buse GAL, Bhandari M, Garutti I, Jacka MJ, Schunemann HJ, Cortes OL, Coriat P, Dvirnik N, Botto F, Pettit S, Jaffe AS and Guyatt GH. Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery. JAMA. 2017;317:1642-1651.

Reference Type: BACKGROUND

1. Halvorsen S, Mehilli J, Cassese S, Hall TS, Abdelhamid M, Barbato E, De Hert S, de Laval I, Geisler T, Hinterbuchner L, Ibanez B, Lenarczyk R, Mansmann UR, McGreavy P, Mueller C, Muneretto C, Niessner A, Potpara TS, Ristic A, Sade LE, Schirmer H, Schupke S, Sillesen H, Skulstad H, Torracca L, Tutarel O, Van Der Meer P, Wojakowski W, Zacharowski K, Group ESCSD, Knuuti J, Kristensen SD, Aboyans V, Ahrens I, Antoniou S, Asteggiano R, Atar D, Baumbach A, Baumgartner H, Bohm M, Borger MA, Bueno H, Celutkiene J, Chieffo A, Cikes M, Darius H, Delgado V, Devereaux PJ, Duncker D, Falk V, Fauchier L, Habib G, Hasdai D, Huber K, Iung B, Jaarsma T, Konradi A, Koskinas KC, Kotecha D, Landmesser U, Lewis BS, Linhart A, Lochen ML, Maeng M, Manzo-Silberman S, Mindham R, Neubeck L, Nielsen JC, Petersen SE, Prescott E, Rakisheva A, Saraste A, Sibbing D, Siller-Matula J, Sitges M, Stankovic I, Storey RF, Ten Berg J, Thielmann M and Touyz RM. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J. 2022.

Reference Type: BACKGROUND

Other Identifiers

GLUMINS

Identifier Type: -

Identifier Source: org_study_id