vasospastic angina pectoris vessel spasm of the coronary artery
Conditions
Interventions
The trial is cross-over placebo controlled. Patients will recieve placebo for 4
weeks and macitentan for 4 weeks while on background (standard) medication. The
order of placebo or macitentan is left
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following inclusion criteria: * Male and female patients * 18 and <75 years old; * Patients with a high frequency (>3 times per week) and duration of anginal complaints, presumed to be caused by VSA; * Absence of significant obstructive coronary artery disease (defined as stenosis > 50% in an epicardial coronary artery) documented by invasive coronary angiography; * Supporting evidence of myocardial ischemia or spasm, defined as either: (a) documented dynamic ECG abnormalities during an episode of angina, or (b) documented troponin rise during an episode of angina, or (c) documented coronary spasm during invasive coronary angiography with or without acetylcholine provocation testing; * Anginal complaints for at least 3 months despite optimal anti-anginal treatment, which is at the discretion of the treating cardiologist. * Signed informed consent
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: * Patients who are pregnant or nursing and those who plan pregnancy in the period up to 1 months after the study; * Women of childbearing potential not using contraception; * Patients with a limited life expectancy less than one year; * Patients unable to provide written informed consent, or are otherwise not suitable for inclusion according to the investigator.Contraindication for macitentan * Patients with active liver disease or severe liver dysfunction with ASAT and/or ALAT >3x upper limit of normal (ULM); * Patients with known renal impairment (GFR<60 ml/min); * Patients with anemia; * Use of potent CYP3A4 inducers (rifampicin, St. John's wort, carbamazepine, phenytoin) due to reduced efficacy of macitentan. * Use of potent CYP3A4 inhibitors (itraconazole, ketoconazole, voriconazole, clarithromycin, ritonavir, saquinavir). en.l",
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The burden of anginal complaints, calculated as: 1. the duration (in minutes) * severity (on a VAS scale 1-10) during the study period up to 2 weeks after discontinuation of the study medication; 2. the frequency of angina attacks * severity (on a VAS scale 1-10) during the study period up to 2 weeks after discontinuation of the study medication. | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy endpoint: * Incidence and severity of angina complaints as obtained by the Seattle Angina Questionnaire during the study period up to 2 weeks after discontinuation of the study medication. Safety endpoints: * Detrimental changes in physical, laboratory or ECG parameters during the study period up to 2 weeks after discontinuation of the study medication. * The occurrence of adverse events (i.e. hospitalization for anginal symptoms and/or myocardial infarction) during the study period up to 2 weeks after discontinuation of the study medication. All possible side effects will be recorded during the study period up to 2 weeks after discontinuation of the study medication. | — |
Countries
Netherlands
Outcome results
None listed