Efficacy of Endothelin Receptor Antagonism in Treatment of Coronary Artery Spasm: a Randomized Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 100
- 试验地点
- 4
- 主要终点
- Successful treatment
研究概览
简要总结
The goal of this randomized clinical trial is to assess if adjunctive bosentan therapy, in comparison to placebo, can reduce the rate of epicardial vasospasm at follow-up spasm provocation CFT (fuCFT) in patients with previously proven epicardial vasospasm on acetylcholine reactivity testing (at index CFT) and ongoing angina(-like) complaints.
Participants will
- Use either endothelin receptor antagonist or placebo for 10 weeks
- Undergo follow-up acetylcholine spasm provocation test after 10 weeks
- Answer online questionnaires on angina and quality of life
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
- Triple (Participant, Care Provider, Investigator)
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
- •Definitive diagnosis of epicardial vasospasm on maximal acetylcholine dose of 100µg (at iCFT)
- •At least 18 years of age
- •On optimal regular care ( current or previous treatment with at least 2 daily anti-anginal medicines i.e. nitrate and calcium channel blocker
- •Continuing episodes of angina(-like) complaints at least once weekly despite
- •Signed online informed consent for participation in NL-CFT registry (the Netherlands Registry of invasive coronary vasomotor function testing), or willing to co-sign for registry at time of inclusion in EDIT-CAS
- •Written informed consent for EDIT-CAS
排除标准
- •Systolic blood pressure (SBP) <85 mmHg measured at Visit 1
- •Significant hepatic impairment at time of iCFT lab (ASAT/ALAT >3x upper limit of normal (ULN)) or history of liver cirrhosis (Child-Pugh 7-15)
- •Severe anemia (Hb<6.0mmol/L) without identified cause at time of inclusion
- •Patients with limited life expectancy (<1 year)
- •Participation in another randomized clinical study with an use of an Investigational Medicinal Product (IMP) up to one month prior to enrolment.
- •Pregnancy, active desire to become pregnant or unwilling to take adequate* contraceptive measures when of child bearing potential for the duration of 6 months (active medication period + 3 months safety).
- •Known heart failure with reduced ejection fraction<35%
- •Known pulmonary hypertension of any type
- •Potentially dangerous interaction due to the use of another CYP3A4 or CYP2C9 substrate (e.g. ciclosporin A, glibenclamide, fluconazole, rifampicin, tacrolimus/sirolimus, lopinavir/ritonavir)
- •Repeat spasm provocation test deemed unsafe (e.g. allergic reaction at iCFT)
- •Adequate in this case meaning if on hormonal contraceptives, additional measures to be taken (e.g. condom).
研究组 & 干预措施
Bosentan
Bosentan 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks
干预措施: Endothelin Receptor Antagonist (Drug)
Placebo
Placebo 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks
干预措施: Placebo control (Other)
结局指标
主要结局
Successful treatment
时间窗: 10 weeks
On repeat invasive spasm provocation according to Coronary Vasomotor Disorders International Study Group (COVADIS) criteria. Successful treatment is defined as absence of epicardial vasospasm according to COVADIS criteria during repeat spasm provocation test at 10 weeks.
次要结局
- Improvement of anginal complaints(10 weeks)