The Effect of Remote Ischemic Preconditioning on Myocardial Injury After Noncardiac Surgery

Study Overview
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Brief Summary
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This is a multicentre, parallel-group, randomised, sham-controlled, observer blinded trial, assessing the efficacy of remote ischemic preconditioning on preventing myocardial injury after noncardiac surgery.

Detailed Description
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This is a multicentre, randomised, sham-controlled, observer blinded trial. Patients at high clinical risk for cardiovascular events and scheduled to undergo major abdominal surgery will be enrolled. A total of 766 patients are randomised (1:1 ratio) to receive RIPC or no RIPC (control) before anaesthesia induction. RIPC will comprise four alternating cycles of cuff inflation for 5 min to 200 mm Hg and deflation for 5 min. In controls, the identical looking cuff will be placed around the arm but not actually inflated for 40 minutes. The primary outcome was myocardial injury after surgery within three days of surgery. The secondary outcomes were peak plasma hs-cTnT and total hs-cTnT release during the first three days after surgery, hs-cTnT above the prognostically important thresholds, length of hospital stay after surgery, and length of stay in the intensive care unit, myocardial infarction, major adverse cardiovascular events, cardiac-related death and all cause death within 30 days, 6 months, 1 year and 2 years after surgery, postoperative morbidity and adverse events within 30 days after surgery.

Official Title
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The Effect of Remote Ischemic Preconditioning on Myocardial Injury After Noncardiac Surgery in Patients at a High Risk of Cardiac Events

Conditions
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Myocardial Injury, Non-cardiac Surgery, Remote Ischemic Preconditioning

Intervention / Treatment
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* Procedure: Remote ischemic preconditioning
* Procedure: Sham-remote ischemic preconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients at high clinical risk for cardiovascular events; Patients scheduled to undergo major abdominal surgery. Exclusion criteria Immediate or urgent surgery or surgery where there is insufficient time to perform RIPC. Abdominal vascular surgery, such as surgery for abdominal aortic aneurysm Experience of conditions precluding the use of RIPC in both arms Patients who are being treated with drugs, such as sulphonamide or nicorandil With contraindications for anaesthetic regimes required in this trial.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote ischemic preconditioning<br>Transient ischemic ischemia consisting of 5-minute ischemia followed by 5-minute perfusion will occur on the upper arm | Procedure: Remote ischemic preconditioning<br>* Remote ischemic preconditioning will consist of four cycles of 5-minute inflation of an blood pressure cuff on the upper arm to 200 mmHg followed by 5-minute deflation. RIPC will be performed twice, one at approximately 24 hours before anaesthesia and the other at approximately 1 hour before anaesthesia.<br>|
| Sham Comparator: Sham-remote ischemic preconditioning<br>Transient ischemic ischemia will not actually occur on the upper arm | Procedure: Sham-remote ischemic preconditioning<br>* The identical looking cuff will be placed around the upper arm but not actually inflated for 40 minutes. The control device's components and external appearance are identical to that of the RIPC. However, as compared to the RIPC, the blood pressure cuff's line of inflation is disconnected such that the cuff cannot be inflated. Control treatment will be performed twice, one at approximately 24 hours before anaesthesia and the other at approximately 1 hour before anaesthesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial injury after non-cardiac surgery (MINS) | Number of participants with MINS, diagnosed according to the criteria established by the American Heart Association in 2021 | Within the first three days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with the concentration of hs-cTnT reaching/above the prognostically important thresholds | Number of participants with the concentration of hs-cTnT reaching/above the prognostically important thresholds | Within the first three days after surgery | 
| Peak concentration of hs-cTnT within the initial 3 days after surgery | Peak concentration of high-sensitivity cTnT | Within the first three days after surgery | 
| Total hs-cTnT release within the initial 3 days after surgery (area under the curve) | Total hs-cTnT release | Within the first three days after surgery | 
| Length of stay in the intensive care unit | Length of intensive care unit stay | expected 2 days after surgery | 
| Length of postoperative stay | Length of hospital stay after surgery | expected 6 days after surgery | 
| Myocardial infarction | Number of participants with myocardial infarction | Within 30 days, 6 months, 1 year and 2 years of surgery | 
| Major adverse cardiovascular events | Cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke | Within 30 days, 6 months, 1 year and 2 years of surgery | 
| Cardiac-related death | Death related by cardiac reason | Within 30 days, 6 months, 1 year and 2 years of surgery | 
| All deaths | All-cause death after surgery | Within 30 days, 6 months, 1 year and 2 years of surgery | 
| Major postoperative morbidity | Major postoperative morbidity | Within 30 days after surgery | 
| Adverse events | Adverse events | Within 30 days after surgery |