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

Safety and Efficacy of Remote Ischemic Conditioning for Patients Taking Off-pump Coronary Artery Bypass Grafting (IMPROVE): A National, Multi-center, Randomized, Controlled, Open-label, Blinded-endpoint Trial

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. 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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Bypass Grafting; Ischemia-Reperfusion Injury; Remote Ischemic Conditioning
• Intervention / Treatment: Device: Remote ischemic conditioning

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 648
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yang Yan; Phone Number: +86.29.85323869; Email: yangyan3@xjtu.edu.cn
• Study Contact Backup: Name: Li Guoliang; Phone Number: +86.29.85323869; Email: liguoliang_med@163.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • First Affiliated Hospital of Xi'an Jiantong University
      • Contact: Yang Yan; Phone Number: +862985323865; Email: yangyan3@xjtu.edu.cn
      • Contact: Guoliang Li; Phone Number: +862985323865; Email: liguoliang_med@163.com

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RIC group; 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; An automatic programmed blood pressure cuffs will be placed on two upper limbs of the patient and pressurized to 200 mmHg (or at least 20 mmHg higher than the systolic blood pressure if the systolic blood pressure of the patient is above 180 mmHg) with 5 minutes of pressurization and 5 minutes of rest. One pressurization with rest is deemed as one cycle (10 minutes), and 4 cycles will be performed each time (for a total of 40 minutes).
No Intervention: Control group; 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?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total costs	Total costs include CABG surgery, medications, examinations, management of complications during the first hospitalization and subsequent hospital admissions for cardiovascular problems. The data will be obtained from medical records and 3-month follow-up.	3-month after the enrollment.
The incidence of adverse events	Possible adverse events include ischemic pain, tissue damage (such as ulceration, gangrene), headache, bleeding events, neoplasm and accident (such as car accident, suicide) and etc. The data will be recorded from the medical records.	3-month after the enrollment.

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Beijing Anzhen Hospital; Baoji Central Hospital; People's Hospital of Qinghai Province; The Second Hospital of Yulin City
• Investigators: Principal Investigator: Yang Yan, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Actual): November 21, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Reperfusion Injury
• Other Study ID Numbers: XJTU1AF2022LSK-427-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No