Safety and Efficacy of Remote Ischemic Conditioning for Patients Taking Off-pump Coronary Artery Bypass Grafting (IMPROVE)

Study Overview
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Brief Summary
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This IMPROVE trial plans to enroll 648 patients who are diagnosed with coronary artery disease and are going to take off-pump CABG in five centers in China, to access whether RIC can and improve short-term prognosis.

Detailed Description
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Remote ischemic conditioning (RIC) is the process of repeated ischemia and reperfusion in the peripheral vessels, which is proved in reducing IRI in vital organs. However, the effect of RIC in patients undergoing off-pump CABG is still unclear. This IMPROVE trial plans to enroll 648 patients who are diagnosed with coronary artery disease and are going to take off-pump CABG in five centers in China, to access whether RIC can and improve short-term prognosis. Patients will be randomly assigned into RIC group and control group. The primary outcome is the occurrence of the major adverse cardiovascular and cerebrovascular events (MACCE) within the 3-month follow-up. The MACCE is defined as all-cause of death, myocardial infarction, stroke and coronary revascularization surgery.

Official Title
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Safety and Efficacy of Remote Ischemic Conditioning for Patients Taking Off-pump Coronary Artery Bypass Grafting (IMPROVE): A National, Multi-center, Prospective, Randomized, Controlled, Double-blinded Trial

Conditions
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Coronary Artery Bypass Grafting, Remote Ischemic Conditioning

Intervention / Treatment
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* Device: Remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with coronary artery disease and require off-pump CABG surgery. Between 18 and 75 years old; Normal left ventricular systolic function (ejection fraction >40%) and left ventricular end-diastolic internal diameter (<60 mm) in the cardiac ultrasound tests; No or mild heart valve and great vessel abnormalities which do not require surgical intervention; Participants or their authorized relatives agree to participate in the clinical trial and sign the informed consent. Exclusion Criteria: Severe tissue injuries. Myalgia, fractures and other peripheral vascular lesions. Bypass graft being the radial artery. Stenosis or severe malformations of the subclavian, jugular and femoral arteries and veins. Previous vagus nerve trunk dissection or vagus nerve block surgery. Other surgical operations at the same time. Patients with pre-existing severe cardiac insufficiency, acute coronary syndromes, malignant hypertension and cardiogenic shock. Severe coagulation abnormality or severe anemia. Severe mental disorder. Malignant tumors. Pregnant or lactating. Increased risk of treatment for patients, according to investigators. Refuse to sign the informed consent form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIC group<br>In the RIC group, patients will undergo RIC training in the 3 days before and 7 days after the CABG surgery. | Device: Remote ischemic conditioning<br>* An automatic programmed blood pressure cuff will be placed on bilateral upper limbs of the patient and pressurized to 200 mmHg (or at least 20 mmHg above the systolic blood pressure), with 5 minutes of pressurization and 5 minutes of rest. One pressurization with rest is deemed as one cycle, and 4 cycles will be performed each time, for a total of 40 minutes.<br>|
| No Intervention: Control group<br>In the control group, a blood pressure cuff, same as the cuff in the RIC group, will be placed on both upper arms of the patients but only pressurized to 60 mmHg. The rest of the procedures will be the same. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of MACCE | MACCE includes all-cause of death, myocardial infarction, stroke and coronary revascularization surgery. The data will be obtained at 3-month follow-up, according to medical records of all patients. | 3-month after the enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of all-cause of death | The data will be obtained at 3-month follow-up, according to medical records of all patients. | 3-month after the enrollment. | 
| The incidence of myocardial infarction | The data will be obtained at 3-month follow-up, according to medical records of all patients. | 3-month after the enrollment. | 
| The incidence of stroke | The data will be obtained at 3-month follow-up, according to medical records of all patients. | 3-month after the enrollment. | 
| The incidence of coronary revascularization surgery | The data will be obtained at 3-month follow-up, according to medical records of all patients. | 3-month after the enrollment. | 
| The length of postoperative ICU-stay | This outcome includes all days in ICU after the operation of all patients. The data will be recorded from the medical records. | About 3 days after the operation. | 
| The total length of stay in the hospital | This outcome includes all days in the hospital of all patients. The data will be recorded from the medical records. | About 7days after the operation. | 
| Changes of 6-min walk test results | 6-min walk test will be measured by stopwatches and metre rulers. The test assesses the overall response of all systems involved in exercise by measuring the distance the patient walks rapidly on a flat, hard surface over a period of six minutes. | 3-month after the enrollment. |