Different Anti-Spastic Therapy Strategies After CABG Using Radial Artery Grafts

Overview

The Pilot study will be a single-center, randomized, open-label, active-controlled trial. After CABG surgery using Radial Artery Grafts (RA-CABG) and signing the informed consent, all patients will be screened according to the inclusion and exclusion criteria. Estimated 150 patients will be enrolled and randomized by ratio 1:1:1 to receive either Nicorandil (5mg tid po) or Diltiazem (180mg qd po) or Isosorbide Mononitrate (50mg qd po). Follow-up visits will be conducted at Day 7, 28, 84, 168 after surgery. The last evaluation of study endpoints and other adverse events will be at Day 168. The pilot study is designed to explore the angiography outcomes of grafts and cardiovascular outcomes of patients, as well as safety outcomes among different anti-spastic regimens after RA-CABG.

Full Title of Study: “A Randomized Controlled Pilot Trial to Compare the Anti-Spastic Efficacy of Nicorandil, Diltiazem and Isosorbide Mononitrate Oral Therapy for Patients Undergoing Coronary Artery Bypass Grafting Using Radial Artery Grafts”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 2022

Detailed Description

After having signed informed consent (Day 1-3), eligible subjects who have successfully received first RA-CABG surgery (Day 0) will be screened for enrollment. All subjects (150 patients) will be randomized in a 1:1:1 ratio into 3 groups. Group A will receive oral Nicorandil (5mg tid) monotherapy; Group B will receive oral Diltiazem (180mg qd) monotherapy; and Group C will receive Isosorbide Mononitrate (50mg qd) monotherapy. Three groups will continue intervention treatment for 168 days (24 weeks) after RA-CABG surgery. All subjects will receive follow-up visits (clinic visit or phone visit) at Day 7, 28, 84, and 168. All subjects will receive first CCTA (or CAG) to evaluate the graft outcome at Day 7 and second CCTA (or CAG) to evaluate the graft outcome at Day 168 after RA-CABG surgery. And all subjects will be evaluated angina relief based on the Canadian Cardiovascular Society (CCS) angina grading and the Seattle Angina Questionnaire. And the time to first major adverse cardiovascular event (MACE), which include all-cause mortality, myocardial infarction, stroke and unplanned revascularization, will be collected. And other safety outcomes will be evaluated, including the rate of hypotension, the proportion of concomitant medications with ACEI/ARB/ARNI drugs and proportion of SAEs and concerned AEs.

Interventions

  • Drug: Nicorandil
    • oral Nicorandil Tablets 5mg (5mg per tablet) three times daily
  • Drug: Diltiazem Hydrochloride
    • oral Diltiazem Hydrochloride Sustained-release Tables180mg (90 mg per tablet) once daily
  • Drug: Isosorbide Mononitrate 50 mg
    • oral Isosorbide Mononitrate Sustained-release Capsules 50 mg (50mg per capsule) once daily

Arms, Groups and Cohorts

  • Experimental: Nicorandil
    • oral Nicorandil 5mg (Tablets) three times daily for 168 days
  • Active Comparator: Diltiazem Hydrochloride
    • oral Diltiazem 180mg (Sustained-release Tablets) once daily for 168 days
  • Active Comparator: Isosorbide Mononitrate
    • oral Isosorbide Mononitrate 50mg (Sustained-release Capsules) once daily for 168 days

Clinical Trial Outcome Measures

Primary Measures

  • the rate of RA graft failure at Day 7
    • Time Frame: at Day 7
    • CCTA or CAG will be used to evaluate the RA graft outcome at Day 7 after RA-CABG. The definition of RA-graft outcomes will refer to the modified Fitzgibbon classification criteria. When RA-graft outcome conform to the Grade B, O or S, the result will be judged as the graft failure.
  • the rate of RA graft failure at Day 168
    • Time Frame: at Day 168
    • CCTA or CAG will be used to evaluate the RA graft outcome at Day 168 after RA-CABG. The definition of RA-graft outcomes will refer to the modified Fitzgibbon classification criteria. When RA-graft outcome conform to the Grade B, O or S, the result will be judged as the graft failure.

Secondary Measures

  • the time to first Major Adverse Cardiovascular Events (MACE)
    • Time Frame: during the study period (168 days)
    • MACE will include all-cause death, myocardial infarction, stroke and unplanned revascularization.
  • the proportion of subjects with angina recurrence
    • Time Frame: during the study period (168 days)
    • The angina symptoms will be evaluated by Canadian Cardiovascular Society angina grade and Seattle Angina Questionnaires.
  • the proportion of subjects with at least one hypotension occurrence
    • Time Frame: during the study period (168 days)
    • Subjects’ blood pressure will be measured by sitting in the clinic or by using a sphygmomanometer outside the hospital (recorded on the diary card). Systolic blood pressure < 90mmHg or diastolic blood pressure < 60mmHg will be recorded as “hypotension” as defined in the study.
  • the proportion of subjects with ACEI/ARB/ARNI withdrawal
    • Time Frame: during the study period (168 days)
    • The subjects who stop using ACEI/ARB/ARNI ≥20% of the time during the study period will be recorded as “ACEI/ARB/ARNI withdrawal” as defined in the study.
  • the proportion of subjects with serious adverse events (SAEs) and concerned adverse events (AEs)
    • Time Frame: during the study period (168 days)
    • SAE will include death; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; a congenital anomaly/birth defect in the offspring of the patient; judged to be medically significant (including laboratory abnormalities). concerned AEs will include: cardiac arrest, reoperation, incision complications, pulmonary infection, respiratory failure, new atrial fibrillation/atrial flutter, permanent pacemaker implantation, and gastrointestinal hemorrhage.

Participating in This Clinical Trial

Inclusion Criteria

  • Age≥18 years old, – Male or female patients, – Have signed informed consent, – Have successfully received a RA-CABG surgery 1-3 days ago. Exclusion Criteria:

  • Previously experienced an allergy to active ingredients and/or excipients of experimental drugs, – Hypotension (defined as systolic blood pressure < 90mmHg or diastolic blood pressure < 60mmHg) after surgery, – Acute myocardial infarction, pulmonary congestion or cardiogenic shock after surgery, – Concomitant medications with phosphodiesterase-5 inhibitors such as sildenafil, vardenafil, tadalafil, etc, – Pathological sinus node syndrome, degree II or III atrioventricular block without cardiac pacemaker, – With contraindications for coronary computed tomography angiography (CCTA) or coronary arteriography (CAG) examination, such as iodine allergy, etc. note: patients with renal insufficiency or even end-stage receiving hemodialysis but can be tolerated by CCTA or CAG examination (judged by investigators) are eligible for inclusion, – History or evidence of ongoing alcohol or drug abuse, – Life expectancy < 1 year judged by investigators, – Other inappropriate situations judged by investigators .

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ruijin Hospital
  • Collaborator
    • Chugai Pharma China
  • Provider of Information About this Clinical Study
    • Principal Investigator: Qiang Zhao,MD, Vice President of RuijinHospital, Professor and Director, Department of Cardiac Surgery – Ruijin Hospital
  • Overall Official(s)
    • Qiang Zhao, MD.PhD, Principal Investigator, Ruijin Hospital
    • Yunpeng Zhu, MD, Study Director, Ruijin Hospital
  • Overall Contact(s)
    • Qiang Zhao, MD.PhD, +8613701695256, zq11607@rjh.com.cn

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