Clinical trial NCT04310995: Different Anti-Spastic Therapy Strategies After CABG Using Radial Artery Grafts
Official title: Effect of Nicorandil, Diltiazem or Isosorbide Mononitrate for Oral Antispastic Therapy After Coronary Artery Bypass Grafting Using Radial Artery Grafts - a Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Bypass Graft
Radial Artery Grafts
Antispastic Therapy
Pilot Study
Keywords: CABG
Radial artery grafts
Antispastic
Nicorandil
Diltiazem
Isosorbide Mononitrate
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Chugai Pharma China
First posted: 2020-03-17
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 Week 1, 4, 12, and 24 after surgery. The last evaluation of study endpoints and other adverse events will be at Week 24.

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.

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 24 weeks after RA-CABG surgery. All subjects will receive follow-up visits (clinic visit or phone visit) at Week 1, 4, 12, and 24 after surgery.

All subjects will receive first CCTA (or CAG) to evaluate the graft outcome at Week 1 and second CCTA (or CAG) to evaluate the graft outcome at Week 24 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.

Eligibility criteria: 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 .

Primary outcomes:
measure: the rate of RA graft failure at Week 1
timeFrame: at Week 1
measure: the rate of RA graft failure at Week 24
timeFrame: at Week 24
Secondary outcomes:
measure: the time to first Major Adverse Cardiovascular Events (MACE)
timeFrame: within 24 weeks
measure: the proportion of subjects with angina recurrence
timeFrame: within 24 weeks
measure: the proportion of subjects with at least one hypotension occurrence
timeFrame: within 24 weeks
measure: the proportion of subjects with ACEI/ARB/ARNI withdrawal
timeFrame: within 24 weeks
measure: the proportion of subjects with serious adverse events (SAEs) and concerned adverse events (AEs)
timeFrame: within 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
Study officials:
affiliation: Ruijin Hospital
name: Qiang Zhao, MD.PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruijin Hospital
name: Yunpeng Zhu, MD
role: STUDY_DIRECTOR
affiliation: Weill Cornell Medicine NewYork Presbyterian Hospital
name: Mario FL Gaudino, MD
role: PRINCIPAL_INVESTIGATOR
References: