CRIC Combined With MFT for Cardiovascular Adverse Events in Patients With Incomplete Revascularization of CAD (CRCMF)

Chronic Remote Ischemic Conditioning Combined With Mindfulness Therapy for Cardiovascular Adverse Events in Patients With Incomplete Revascularization of Coronary Artery Disease: A Multicenter, Double-blind, Randomized Controlled Trial

The main objective of this study is to demonstrate whether the combination of chronic remote ischemic conditioning and mindfulness therapy can reduce cardiovascular adverse events in patients with incomplete revascularization of coronary artery disease.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: chronic remote ischemic conditioning; Behavioral: Mindfulness Therapy; Other: sham CRIC; Behavioral: sham MFT

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Quan Guo, MD; Phone Number: 15670510031; Email: xinyiguoquan@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Fuwai Central China Cardiovascular Hospital
      • Contact: GUO QUAN, MD; Phone Number: 15670510031; Email: xinyiguoquan@163.com
      • Contact: Email: lmw0207@163.com
      • Principal Investigator: Muwei LI

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1) Age ≥18 years old
• 2) Consistent with the diagnosis of coronary heart disease, complete revascularization was not performed (coronary angiography showed that at least one vessel with a reference diameter of 3.0mm had stenosis greater than 90%, and quantitative flow ratio (QFR) < 0.80)
• 3) Symptoms of myocardial ischemia (resting or exertional angina; Angina allele: chest tightness, shortness of breath, etc.);

Exclusion Criteria:

• Age < 18 years old
• Heart failure patients with NYHA class IV, or left ventricular ejection fraction (LVEF) < 30%
• Creatinine clearance <15 mL/min (or eGFR < 15 mL/min/1.73m²), or requires dialysis
• Myocardial diseases such as hypertrophic cardiomyopathy, dilated cardiomyopathy, etc.
• Uncontrolled or recurrent arrhythmic events (e.g., ventricular fibrillation, recurrent or symptomatic sustained ventricular tachycardia, complete heart block, atrial fibrillation with rapid ventricular rates, supraventricular tachycardia refractory to drugs)
• Poorly controlled hypertension (SBP > 180 mm Hg or DBP > 110 mm Hg)
• Active liver disease or persistent ALT or AST elevation ≥ 3 times the upper limit of normal
• Unexplained CK > 5 times the upper limit of normal, or elevated CK due to known muscle disease
• Planned or anticipated cardiac surgery or revascularization before randomization
• History of active malignancy (surgery, radiation therapy, and/or systemic therapy within the past 3 years)
• Diagnosed or suspected upper extremity vascular malformations, aneurysms, arteriovenous fistulas, or thrombosis
• Hearing impairment, unable to undergo mindfulness therapy
• Currently participating in another drug or device study, or within 30 days of completing another drug or device study or receiving another investigational drug
• Any life-threatening comorbid conditions expected to result in death within the next year (excluding cardiovascular diseases)
• Alcoholism, substance abuse history; and unwilling or unable to stop alcohol or substance abuse during the study
• History of major organ transplant (e.g., lung, liver, heart, bone marrow, kidney)
• Investigator's judgment of known major active and uncontrolled disease, or any medical, physical, or surgical conditions (e.g., infection, significant blood, kidney, metabolic, gastrointestinal, or endocrine dysfunction) that may interfere with participation in the clinical study
• As known to the investigator, the subject is unlikely to complete follow-up for more than 1 year or is expected to be unable to comply with the study requirements or understand the study's objectives and potential risks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CRIC+MFT; CIRC: Using a semi-automated machine, the pressure is increased according to the patient's own blood pressure level (20-40mmHg) when the cuff is pressed, and the pressure is compressed for 6 minutes per cycle, and the rest is 4 minutes per cycle. MFT: Participants receive guided mindfulness audio sessions twice daily for ~30 minutes each throughout the perioperative period. Content includes standardized mindfulness practices (e.g., focused attention, body awareness, nonjudgmental observation) designed to reduce anxiety and improve sleep quality.	Device: chronic remote ischemic conditioning; Using a semi-automated machine, the pressure is increased according to the patient's own blood pressure level (20-40mmHg) when the cuff is pressed, and the pressure is squeezed for 6 minutes per cycle and the rest is 4 minutes, for a total of 4 cycles per cycle.; Other Names: CRIC; Behavioral: Mindfulness Therapy; Participants receive guided mindfulness audio sessions twice daily for ~30 minutes each throughout the perioperative period. Content includes standardized mindfulness practices (e.g., focused attention, body awareness, nonjudgmental observation) designed to reduce anxiety and improve sleep quality.; Other Names: MFT
Sham Comparator: Control (neither CRIC nor MFT).; Sham CRIC: The pressure was 60mmHg when the cuff was pressurized, and the other modes were the same as in the CIRC group. Sham MFT: Health Education + Relaxation (HER): A time- and attention-matched audio program (twice daily, 30 minutes) delivering perioperative recovery and sleep-hygiene education with passive relaxation (music or simple muscle loosening), excluding mindfulness-specific techniques (no present-moment/nonjudgmental awareness training, no breath-focused meditation, no open monitoring).	Other: sham CRIC; The pressure was 60mmHg when the cuff was pressurized, and the other modes were the same as those of the CIRC group.; Behavioral: sham MFT; Sham MFT: Health Education + Relaxation (HER): A time- and attention-matched audio program (twice daily, 30 minutes) delivering perioperative recovery and sleep-hygiene education with passive relaxation (music or simple muscle loosening), excluding mindfulness-specific techniques (no present-moment/nonjudgmental awareness training, no breath-focused meditation, no open monitoring).
Sham Comparator: CRIC+sham MFT; CIRC: Using a semi-automated machine, the pressure is increased according to the patient's own blood pressure level (20-40mmHg) when the cuff is pressed, and the pressure is compressed for 6 minutes per cycle, and the rest is 4 minutes per cycle. Sham MFT-Health Education + Relaxation (HER): A time- and attention-matched audio program (twice daily, 30 minutes) delivering perioperative recovery and sleep-hygiene education with passive relaxation (music or simple muscle loosening), excluding mindfulness-specific techniques (no present-moment/nonjudgmental awareness training, no breath-focused meditation, no open monitoring).	Device: chronic remote ischemic conditioning; Using a semi-automated machine, the pressure is increased according to the patient's own blood pressure level (20-40mmHg) when the cuff is pressed, and the pressure is squeezed for 6 minutes per cycle and the rest is 4 minutes, for a total of 4 cycles per cycle.; Other Names: CRIC; Behavioral: sham MFT; Sham MFT: Health Education + Relaxation (HER): A time- and attention-matched audio program (twice daily, 30 minutes) delivering perioperative recovery and sleep-hygiene education with passive relaxation (music or simple muscle loosening), excluding mindfulness-specific techniques (no present-moment/nonjudgmental awareness training, no breath-focused meditation, no open monitoring).
Sham Comparator: Sham CRIC+MFT; Sham CRIC: The pressure was 60mmHg when the cuff was pressurized, and the other modes were the same as in the CIRC group. MFT: Participants receive guided mindfulness audio sessions twice daily for ~30 minutes each throughout the perioperative period. Content includes standardized mindfulness practices (e.g., focused attention, body awareness, nonjudgmental observation) designed to reduce anxiety and improve sleep quality.	Behavioral: Mindfulness Therapy; Participants receive guided mindfulness audio sessions twice daily for ~30 minutes each throughout the perioperative period. Content includes standardized mindfulness practices (e.g., focused attention, body awareness, nonjudgmental observation) designed to reduce anxiety and improve sleep quality.; Other Names: MFT; Other: sham CRIC; The pressure was 60mmHg when the cuff was pressurized, and the other modes were the same as those of the CIRC group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of MACE	Clinical events were defined as: cardiac death, nonfatal myocardial infarction, hospitalization for new heart failure, hospitalization for angina pectoris	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Cardiac Death	Death is considered cardiac unless there is clear evidence of non-cardiac death	3，6，9，12，24months
Incidence of Non-fatal Myocardial Infarction	Includes STEMI and NSTEMI with elevated serum troponin on the basis of patient symptoms or ECG changes	3，6，9，12，24months
Incidence of hospitalisation for new-onset heart failure	New onset of heart failure-related symptoms with elevated serum BNP or NT-ProBNP	3，6，9，12，24months
Incidence of hospitalised for angina pectoris	Hospitalisation for angina pectoris symptoms of all causes, with a discharge diagnosis of angina pectoris	3，6，9，12，24months
Incidence of unplanned revascularisation	Unplanned revascularisation	3，6，9，12，24months
Incidence of all cause death	Death from any cause	3，6，9，12，24months
Incidence of total length of hospitalization due to coronary heart disease	Refers to the number of days when all hospitalizations for all causes of coronary heart disease are stacked together	3，6，9，12，24months
Medical expenses due to coronary heart disease	Refers to medical expenses incurred as a result of coronary heart disease	3，6，9，12，24months
Degree of improvement in angina symptoms	The degree of improvement in angina symptoms will be assessed using the Seattle Angina Questionnaire (SAQ), a 19-item self-administered questionnaire that evaluates five domains of health status in patients with coronary artery disease: physical limitation (9 items), angina stability (1 item), angina frequency (2 items), treatment satisfaction (4 items), and disease perception (3 items). Each domain score ranges from 0 to 100, with higher scores indicating better function (e.g., less physical limitation, less frequent angina, and better quality of life). A summary score, averaging the physical limitation, angina frequency, and quality of life domains, also ranges from 0 to 100. Improvement will be measured as the change in SAQ domain scores and summary score from baseline to follow-up time points, where an increase of 10 points or more in any domain or the summary score is considered clinically significant.	3，6，9，12，24months
Change in anxiety scores	Changes in anxiety scores will be assessed using the Zung Self-Rating Anxiety Scale (SAS), a 20-item self-report questionnaire that measures anxiety symptoms across cognitive, autonomic, motor, and central nervous system domains. Each item is rated on a 4-point Likert scale (1 = "none or a little of the time" to 4 = "most or all of the time"), yielding a raw total score ranging from 20 to 80, with higher scores indicating greater anxiety severity. Raw scores can be converted to an index score by multiplying by 1.25 (range: 25 to 100). The change in anxiety scores will be calculated as the difference in raw SAS scores from baseline to follow-up time points. For reference, raw scores are typically interpreted as: <36 (normal), 36-47 (mild anxiety), 48-59 (moderate anxiety), and ≥60 (severe anxiety).	3，6，9，12，24months
Change in depression scores	Changes in depression scores will be assessed using the Zung Self-Rating Depression Scale (SDS), a 20-item self-report questionnaire that measures depressive symptoms across affective, psychological, and somatic domains. Each item is rated on a 4-point Likert scale (1 = "none or a little of the time" to 4 = "most or all of the time"), yielding a raw total score ranging from 20 to 80, with higher scores indicating greater depression severity. Raw scores can be converted to an index score by multiplying by 1.25 (range: 25 to 100). The change in depression scores will be calculated as the difference in raw SDS scores from baseline to follow-up time points. For reference, raw scores are typically interpreted as: <40 (normal), 40-47 (mild depression), 48-55 (moderate depression), and ≥56 (severe depression).	3，6，9，12，24months
Changes in sleep quality	Changes in sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a 19-item self-report questionnaire that evaluates sleep quality over the past month across seven components: subjective sleep quality (1 item), sleep latency (2 items), sleep duration (1 item), habitual sleep efficiency (3 items), sleep disturbances (9 items), use of sleeping medication (1 item), and daytime dysfunction (2 items). Each component is scored from 0 to 3, with higher scores indicating greater dysfunction. The global PSQI score is the sum of the seven components and ranges from 0 to 21, with higher scores indicating poorer sleep quality. Changes in sleep quality will be calculated as the difference in global PSQI scores from baseline to follow-up time points. For reference, a global score >5 is indicative of poor sleep quality.	3，6，9，12，24months

Collaborators and Investigators

• Sponsor: Henan Institute of Cardiovascular Epidemiology
• Investigators: Study Chair: Muwei LI, MD, Fuwai Central China of Cardiovascular Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): February 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease
• Other Study ID Numbers: HenanICE202501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Main research content 2 years after the publication of the paper
• IPD Sharing Access Criteria: It is available on reasonable request from the contact person for the study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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