Clinical trial NCT04779008: Long-term Remote Ischemic Preconditioning Improves Myocardial Perfusion and Prognosis of Patients After CABG
Official title: Long-term Remote Ischemic Preconditioning Improves Myocardial Perfusion and Prognosis of Patients After Coronary Artery Bypass Grafting
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Coronary Disease
Lead sponsor: Henan Institute of Cardiovascular Epidemiology
Sponsor class: OTHER
First posted: 2021-03-03
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental Group 1:The patient underwent one RIPC (Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff air vehicle to 200 mmHg) 4 hours before surgery, then normal surgery, and RIPC was performed on the second day after surgery and every day after surgery, which lasted for 1 year.

Experiment Group 2: Patients underwent once RIPC 4 hours before surgery, and then normal medical procedures were performed with no additional intervention.

Control group: Patients did not receive any additional intervention.
Primary purpose: TREATMENT

Brief summary: Remote Ischemic preconditioning (RIPC) has been reported to improve myocardial microcirculation, promote collateral circulation recruitment, and improve myocardial perfusion in patients.Two large randomized controlled trials demonstrated a perioperative cardioprotective effect of RIPC (reduced troponin levels), but did not find that a single preoperative RIPC improved long-term outcomes of coronary artery bypass grafting(CABG).The effect of a single RIPC before CABG may be too short. This study aims to investigate whether long-term RIPC improved myocardial perfusion in patients 3 months and 6 months after CABG surgery , and to detect changes in blood vascular endothelial growth factor, Nitrc Oxide, adenosine，and Endothelin-1, and to observe MACCE event rates at 12 months.

Detailed description: A total of 210 patients were randomly divided into three groups according to the inclusion and exclusion criteria, with 70 patients in each group.

Experimental Group 1:

The patient underwent one RIPC (Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff air vehicle to 200 mmHg) 1 hours before surgery, then normal surgery, and RIPC was performed on the second day after surgery and every day after surgery, which lasted for 1 year.

Experiment Group 2:

Patients underwent once RIPC 1 hours before surgery, and then normal medical procedures were performed with no additional intervention.

Control group:

Patients did not receive any additional intervention. All patients were evaluated in three ways. First: 7days and 3 months after surgery , the quantitative examination of myocardial blood flow was conducted to observe the improvement of myocardial blood perfusion.

Second: The changes in the concentrations of vascular colorectal growth factor, Nitrc Oxide, adenosine, and endothelin-1.

Third, patients were evaluated for 6 months and 12months MACCE incidence (cardiovascular death, Nonfatal myocardial infarction, unplanned revascularization, and stroke).

Eligibility criteria: Inclusion Criteria:

* Three coronary artery lesions, CABG surgery was planned

Exclusion Criteria:

* The patients could not tolerate ripc;
* peripheral vascular disease affecting upper limbs
* Acute myocardial infarction complicated with cardiogenic shock，in recent 30 days,
* Emergency cases
* Severe structural heart disease and severe arrhythmia ；
* The uncontrolled systolic blood pressure and diastolic blood pressure of severe hypertension were 180 mmHg and 120 mmHg respectively;
* Severe liver, renal and pulmonary disease
* Mental disorder can't cooperate;
* Inability to give informed consent；
* Patients on glibenclamide or nicorandil, as these medications may interfere with RIC
* pregnant;

Primary outcomes:
measure: Change of MBF by SPECT
timeFrame: 3 months
measure: Change of MPR by SPECT
timeFrame: 3 months
measure: Change of MBF by CE
timeFrame: 3 months
measure: Change of MPR by CE
timeFrame: 3 months
Secondary outcomes:
measure: MBF by SPECT
timeFrame: 1 weeks
measure: MPR by SPECT
timeFrame: 1 weeks
measure: MBF by CE
timeFrame: 1 weeks
measure: MPR by CE
timeFrame: 1 weeks
measure: Rate of major adverse cardiovascular and cerebrovascular events
timeFrame: 12 months
measure: Rate of major adverse cardiovascular and cerebrovascular events
timeFrame: 6 months
measure: Concentration of VEGF
timeFrame: -1days，1 weeks，3months post surgery
measure: Concentration of NO
timeFrame: -1days，1 weeks，3months post surgery
measure: Concentration of BK
timeFrame: -1days，1 weeks，3months post surgery
measure: Concentration of ET-1
timeFrame: -1days，1 weeks，3months post surgery
measure: Concentration of adenosine
timeFrame: -1days，1 weeks，3months post surgery
measure: Concentration of troponin
timeFrame: Before surgery and after surgery
measure: 6 minute Walk Test
timeFrame: 1 weeks, 3/6/9 and 12 months post surgery
measure: Seattle angina questionnaire score
timeFrame: 1 weeks, 3/6/9 and 12 months post surgery
measure: Change of LVEF by SPECT
timeFrame: 1 weeks, 3 months,6 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Fuwai central China cardiovascular Hospital
state: Henan
Study officials:
affiliation: Fuwai central China cardiovascular hospotial
name: Muwei Li, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Fuwai central China cardiovascular hospotial
name: Zhaoyun Cheng, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.
citation: Lau JK, Roy P, Javadzadegan A, Moshfegh A, Fearon WF, Ng M, Lowe H, Brieger D, Kritharides L, Yong AS. Remote Ischemic Preconditioning Acutely Improves Coronary Microcirculatory Function. J Am Heart Assoc. 2018 Oct 2;7(19):e009058. doi: 10.1161/JAHA.118.009058.
citation: Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schon J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Hasenclever D, Zacharowski K; RIPHeart Study Collaborators. A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery. N Engl J Med. 2015 Oct 8;373(15):1397-407. doi: 10.1056/NEJMoa1413579. Epub 2015 Oct 5.
citation: Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.