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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- the rate of RA graft failure at Week 1
研究概览
简要总结
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.
The original study plan included a 24-week follow-up to evaluate the effects of different antispasmodic medications on radial artery grafts. The study protocol has been updated to include a centralized follow-up at a median of 5 years post-surgery. During this follow-up, patients' survival status, imaging results of graft vessels, and major cardiovascular events will be collected via outpatient visits or telephone interviews, with the aim of evaluating the impact of different antispasmodic strategies on long-term clinical outcomes and graft patency.
详细描述
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.
This 5-year extended follow-up study plans to conduct centralized follow-up visits (outpatient or telephone) with study participants. Data to be collected during the follow-up include: survival status (if deceased, date and cause of death), all CCTA or CAG results obtained from the time of surgery up to this follow-up visit, all clinical events meeting the definition of study endpoints and their date of occurrence, medical records related to clinical events (e.g., outpatient records, discharge summaries, laboratory results, imaging reports), and current concomitant medication information. For deceased patients, death and cause of death will first be determined by telephone interview with relatives. If available, relevant medical records will be obtained from their relatives to further ascertain the cause of death.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age≥18 years old，
- •Male or female patients，
- •Have signed informed consent，
- •Have successfully received a RA-CABG surgery 1-3 days ago.
排除标准
- •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 .
研究组 & 干预措施
Diltiazem
干预措施: Diltiazem 180mg qd (Drug)
Nicorandil
干预措施: Nicorandil 5mg tid (Drug)
Isosorbide Mononitrate
干预措施: Isosorbide Mononitrate 50mg qd (Drug)
结局指标
主要结局
the rate of RA graft failure at Week 1
时间窗: at Week 1
CCTA or CAG will be used to evaluate the RA graft outcome at Week 1 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 Week 24
时间窗: at Week 24
CCTA or CAG will be used to evaluate the RA graft outcome at at Week 24 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.
次要结局
- the time to first Major Adverse Cardiovascular Events (MACE)(within 24 weeks)
- the proportion of subjects with at least one hypotension occurrence(within 24 weeks)
- the proportion of subjects with ACEI/ARB/ARNI withdrawal(within 24 weeks)
- the proportion of subjects with angina recurrence(within 24 weeks)
- the proportion of subjects with serious adverse events (SAEs) and concerned adverse events (AEs)(within 24 weeks)
- Time to First Radial Artery Graft Failure during Extended Follow-up(within the extended follow-up period (median follow-up of 5 years).)
- Time to First Composite Event during Extended Follow-up(within the extended follow-up period (median follow-up of 5 years).)
研究者
Qiang Zhao,MD
Vice President of RuijinHospital, Professor and Director, Department of Cardiac Surgery
Ruijin Hospital