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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06324461
Other study ID # GLUMINS
Secondary ID
Status Not yet recruiting
Phase Phase 4
First received
Last updated
Start date March 20, 2024
Est. completion date December 31, 2027

Study information

Verified date March 2024
Source The University of Hong Kong
Contact Chun Ka Wong, Clinical Assistant Professor
Phone +852 2255 3597
Email wongeck@hku.hk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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 4 days prior to surgery or receive routine care. Semaglutide (Ozempic; Novo Nordisk, Denmark) 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 372
Est. completion date December 31, 2027
Est. primary completion date December 31, 2026
Accepts healthy volunteers No
Gender All
Age group 45 Years and older
Eligibility Inclusion Criteria: - Age = 45 years - Planned elective non-cardiac laparotomy, thoracotomy, laparoscopic or thoracoscopic 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 - Current use of Dipeptidyl peptidase-4 inhibitor(DPP4i), including Sitagliptin, Linagliptin and Vildagliptin

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Semaglutide 0.25mg subcutaneous injection
Subject randomized into treatment group will receive single subcutaneous dose of Semaglutide 0.25mg 1 to 4 days prior to surgery

Locations

Country Name City State
China Queen Mary Hospital Hong Kong Hong Kong SAR

Sponsors (1)

Lead Sponsor Collaborator
The University of Hong Kong

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Other Proportion of patients with coronary revascularization Within 30 days of randomization
Other Proportion of patients who require readmission for cardiovascular conditions Within 30 days of randomization
Other Proportion of patients with non-fatal cardiac arrest Within 30 days of randomization
Other Proportion of patients who require hospitalization for heart failure Within 30 days of randomization
Other Proportion of patients who develop pulmonary embolism and/or deep vein thrombosis Within 30 days of randomization
Other Proportion of patients with International Society on Thrombosis and Haemostasis (ISTH) major bleeding Within 30 days of randomization
Other Proportion of patients with bleeding independently associated with mortality following noncardiac surgery (BIMS) Within 30 days of randomization
Other Proportion of patients with infection or sepsis Within 30 days of randomization
Other Proportion of patients with acute renal failure fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria Within 30 days of randomization
Other Proportion of patients with acute renal failure requiring dialysis Within 30 days of randomization
Other Proportion of patients requiring amputation Within 30 days of randomization
Other Mean length of stay During index hospitalization up to 3 days
Other Mean length of intensive care unit stay During index hospitalization up to 1 week
Other Mean days alive without need for intensive care support During index hospitalization up to 3 days
Primary Proportion of patients with MINS Defined as any elevation in troponin T >= 14ng/L Within 72 hours after surgery
Secondary Proportion of patients with composite of non-fatal MINS, non-fatal stroke or cardiovascular mortality Within 30 days of randomization
Secondary Proportion of patients with MINS who do not fulfill the 4th universal definition of myocardial infarction Within 30 days of randomization
Secondary Proportion of patients with myocardial infarction according to the 4th universal definition of myocardial infarction Within 30 days of randomization
Secondary Proportion of patients with ischemic stroke Within 30 days of randomization
Secondary Proportion of patients with cardiovascular death Within 30 days of randomization
Secondary Proportion of patients with all-cause mortality Within 30 days of randomization
Secondary Mean days alive and out of hospital Within 30 days of randomization
Secondary Clinically important atrial fibrillation Within 30 days of randomization
Secondary Clinically significant hypoglycaemia Within 30 days of randomization
Secondary Mean peak troponin T concentration During the period of index hospitalization up to 3 days
Secondary Mean area under curve of troponin T concentration During the period of index hospitalization up to 3 days
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