SecondarY Prevention and maNagement of Myocardial Injury aftER Noncardiac surGerY (SYNERGY) Pilot Trial

A Pilot Pragmatic Randomized Controlled Trial Evaluating Secondary Cardiovascular Prevention Therapies in Patients Who Had a Myocardial Injury After Noncardiac Surgery to Prevent Major Cardiovascular Events

Cardiac complications, particularly myocardial injury after noncardiac surgery (MINS), significantly contribute to 30-day mortality, affecting about 1 in 10 patients after noncardiac surgery. Despite its prevalence and serious implications, there is no consensus on managing myocardial injury after noncardiac surgery in clinical practice. Interventions commonly used for cardiovascular prevention in patients who had a heart attack outside of a surgery context could also be beneficial in patient with MINS. This pilot study trial aims to gather feasibility data, such as recruitment rates and intervention adherence that will guide on the design and inform on sample size of a future study with large pragmatic randomized controlled trial on the impact of systematic referral for secondary cardiovascular prevention on outcomes in patients who had a MINS.

Study Overview

• Status: Not yet recruiting
• Conditions: Myocardial Injury After Noncardiac Surgery (MINS)
• Intervention / Treatment: Procedure: Intervention Group

Detailed Description

The SYNERGY study is a pilot randomized controlled trial with 100 patients who had myocardial injury after noncardiac surgery (MINS). Patients are assigned to either a control group receiving usual care or an intervention group that receives referral to a specialist for implementations of interventions on secondary cardiovascular prevention. Secondary cardiovascular prevention will be individualized to the patient's risk factors and may include antiplatelet agents, cholesterol-lowering treatment, blood pressure-lowering medication, as well as counselling on healthy lifestyle choices on diet and exercise, including, if applicable, optimization of diabetes treatment and help in quitting smoking.

At six months, follow-up will assess clinical cardiovascular outcomes, medication adherence, smoking status, adherence to a Mediterranean diet and physical activity.

Key feasibility metrics include recruitment rate, intervention adherence, crossover in the control group, and changes physical activity and dietary pattern. This study aims to address untreated myocardial injury after noncardiac surgery by collecting feasibility data to inform on the design of a future large randomized clinical trials on secondary cardiovascular prevention.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Melodie Boko, MSc; Phone Number: 31541 514-890-8000; Email: synergy.dri.chum@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C1
      • Centre Hospitalier de l'Université de Montréal
      • Contact: Emmanuelle Duceppe, MD PhD; Phone Number: 514-890-8000; Email: emmanuelle.duceppe.med@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have undergone noncardiac surgery,
2. Had a myocardial injury after noncardiac surgery with a presumed ischemic mechanism and without an overt nonischemic precipitating etiology (e.g., sepsis)
3. Provide written informed consent to participate in the SYNERGY pilot trial.

Exclusion Criteria:

1. already on 2 of 3 secondary cardiovascular prevention medications (i.e., antiplatelet, statin, and/or angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)
2. patients with contraindication to statins (i.e., decompensated or Child-Pugh C cirrhosis, acute liver failure, elevated AST/ALT greater than 2-fold the normal upper limit, previous demonstrated statin hypersensitivity, allergy, or statin-related myopathy);
3. patients with contraindication to antiplatelet therapy (i.e., active or recent <1-month peptic ulcer disease, esophageal or gastric variceal disease, history of intracranial or intraspinal hemorrhage, significant thrombocytopenia with platelet count <50 × 109/L),
4. patients with contraindication to ACEI and ARB therapy (i.e, hypersensitivity or allergy to ACEI or ARB);
5. Previously enrolled in the SYNERGY pilot trial,
6. Considered unreliable or unable to complete the trial procedures.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care; Patients who had myocardial injury after noncardiac surgery are assigned to receive usual care.
Active Comparator: Systematic referral for secondary cardiovascular prevention; Systematic referral to an internist within 6 weeks after myocardial injury after noncardiac surgery for implementation of secondary cardiovascular prevention strategies, individualized the patient's risk factors.	Procedure: Intervention Group; Patients being referred to an internist or cardiologist after myocardial injury after noncardiac surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average recruitment rate	Average number of patients recruited per month. Feasibility is defined as average recruitment rate ≥3 patients/month/site as "trial feasible", between 1-2 patients/month/site as "potentially feasible with protocol modifications", and <1 patient/month/site as "unlikely feasible".	12 months
Proportion adherence to referral to specialized cardiovascular care in the intervention group	Defined as the proportion of patients allocated to the intervention group with referral to internal medicine or cardiology within 6 weeks of MINS. The adherence feasibility outcome is defined as follows: ≥70% as "trial feasible", between 40-69% "potentially feasible with protocol modifications", and <40% "unlikely feasible".	6 months
Proportion crossover to referral to specialized CV care in the control group	Defined as the proportion of patients allocated to the control group with referral to internal medicine or cardiology within 6 weeks of MINS. The crossover feasibility outcome is defined as follows: <30% as "trial feasible", between 30-49% "potentially feasible with protocol modifications", and >50% "unlikely feasible".	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of prescription of cardiovascular medications	Proportion of patients who are prescribed an antiplatelet, statin, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blockers (ARB) (all three) at 6 months.	6 months
Proportion of patients on antiplatelet therapy	Proportion of patients who are prescribed an antiplatelet therapy.	6 months
Proportion of patients on statin therapy	Proportion of patients who are prescribed a statin.	6 months
Proportion of patients on angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)	Proportion of patients who are prescribed an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB).	6 months
Proportion consent of eligible patients	Proportion of eligible patients which consented to participate in the trial	12 months
Proportion of completeness to follow-up	Proportion of patients enrolled in the trial that completed the 6-month follow-up	6 months
Change in IPAQ score	Difference in physical activity score (i.e., the short form of the International Physical Activity Questionnaire (IPAQ-SF) score in metabolic equivalents (METs) minute per week) between baseline and 6 months, expressed as a continuous outcome, with higher values meaning a larger increase in physical activity level.	6 months
Change in MEDAS score	Difference between the Mediterranean Diet Adherence Screener (MEDAS) questionnaire score at baseline and 6 months (score between 0 and 14, with high score reflecting higher adherence).	6 months
Proportion of major cardiovascular events	Proportion of patients who experience any of the following composite of cardiovascular death, non-fatal cardiac arrest, myocardial infarction, stroke, heart failure, and coronary revascularization.	6 months
Proportion of cardiovascular death	Proportion of patients with a cardiovascular death is defined as any death with a cardiovascular cause and includes those deaths following a myocardial infarction, sudden cardiac arrest, stroke, cardiac revascularization procedure (i.e., percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery), and heart failure.	6 months
Proportion of myocardial infarction	Proportion of patients with a myocardial infarction as defined according to the Fourth Universal Definition of Myocardial Infarction.	6 months
Proportion of non-fatal cardiac arrest	Proportion of patients with a nonfatal cardiac arrest defined as successful resuscitation from either documented or presumed ventricular fibrillation, sustained ventricular tachycardia, asystole, or pulseless electrical activity requiring cardiopulmonary resuscitation, pharmacological therapy, or cardiac defibrillation.	6 months
Proportion of coronary revascularization	Proportion of patients with a cardiac revascularization procedures including percutaneous coronary intervention (PCI) and coronary arterial bypass grafting (CABG).	6 months
Proportion of stroke	Proportion of patients with a stroke defined as either: a new focal neurological deficit thought to be vascular in origin with signs or symptoms lasting more than 24 hours or leading to death, OR; a new focal neurological deficit thought to be vascular in origin with signs or symptoms lasting less 24 hours with a positive neuroimaging consistent with a stroke.	6 months
Proportion of transient ischemic attack	Proportion of patients with a transient ischemic attack defined as rapidly developed and transient clinical signs of focal or global disturbance of cerebral function, lasting less than 24 hours, with either 1) direct weighted magnetic resonance findings of acute brain ischemic lesions, or 2) high risk neurologic features (i.e., lateralizing weakness and/or speech disruption lasting >5 min).	6 months
Proportion of heart failure	Proportion of patients with a diagnosis of heart fialure, as defined by (criteria A and B required): A. New or worsening symptoms due to heart failure (HF), including at least ONE of the following: 1. Shortness of breath (dyspnea with exertion, dyspnea at rest, orthopnea, paroxysmal nocturnal dyspnea), 2. Decreased exercise tolerance, or 3. Fatigue. B. Signs of new or worsening HF, consisting of at least TWO physical examination findings OR one physical examination finding and at least ONE laboratory (i.e., natriuretic peptide elevation) or radiological imaging.	6 months
Proportion of all-cause mortality	Proportion of patients who died of any cause.	6 months
Proportion of new significant arrythmia	Proportion of patients with a new significant arrythmia defined as new supraventricular or ventricular arrythmia that results in angina, congestive heart failure, symptomatic hypotension, or that requires oral or intravenous treatment with a rate controlling drug, antiarrhythmic drug, electrical cardioversion, implantation of a pacemaker or implantable cardioverter defibrillator.	6 months
Proportion of major bleeding	Proportion of patients with a major bleeding defined according to the criteria of International Society on Thrombosis and Haemostasis (ISTH) as clinically overt bleeding which was fatal or associated with any of the following: a fall in hemoglobin level of 2 g/dL or more or documented transfusion of at least 2 units of packed red blood cells,; involvement of a critical anatomical site (intracranial, spinal, ocular, pericardial, articular, intramuscular with compartment syndrome, retroperitoneal).	6 months
Proportion of clinically relevant non-major bleeding	Proportion of patients with a clinically relevant non-major bleeding defined as any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: requiring medical intervention by a healthcare professional; leading to hospitalization or increased level of care; prompting a face to face (i.e., not just a telephone or electronic communication) evaluation	6 months
Proprotion of kidney injury	Proportion of patients with a kidney Injury defined by the Acute Kidney Injury Network (AKIN) definition and classified according to the following stage: Stage 1: Serum creatinine increase ≥26.5 μmol/l or increase to 1.5-2.0-fold from baseline Stage 2: Serum creatinine increase >2.0-3.0-fold from baseline Stage 3: Serum creatinine increase >3.0-fold from baseline or serum creatinine ≥354 μmol/l with an acute increase of at least 44 μmol/l or need for new renal replacement therapy.	6 months
Proportion of liver injury	Proportion of patients with a liver injury defined by elevation of ALT and/or AST ≥3 times the upper limit of normal.	6 months
Proportion of rhabdomyolysis	Proportion of patients with a rhabdomyolysis defined as muscle symptoms with serum creatinine kinase ≥10 times the upper limit of normal.	6 months

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Heart and Stroke Foundation of Canada
• Investigators: Principal Investigator: Emmanuelle Duceppe, MD PhD, Centre hospitalier de l'Université de Montréal (CHUM)

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Noncardiac surgery; Secondary cardiovascular prevention
• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: 2024-12117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No