Vasospastic angina treatment by Endothelin Receptor Antagonism; a proof of concept study

Phase 4

Completed

Conditions: vasospastic angina pectoris
vessel spasm of the coronary artery
10011082

Registration Number: NL-OMON55720

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 30

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

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).
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Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The burden of anginal complaints, calculated as:<br /><br>1. the duration (in minutes) * severity (on a VAS scale 1-10) during the study<br /><br>period up to 2 weeks after discontinuation of the study medication;<br /><br>2. the frequency of angina attacks * severity (on a VAS scale 1-10) during the<br /><br>study period up to 2 weeks after discontinuation of the study medication.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Efficacy endpoint:<br /><br>* Incidence and severity of angina complaints as obtained by the Seattle Angina<br /><br>Questionnaire during the study period up to 2 weeks after discontinuation of<br /><br>the study medication.<br /><br><br /><br>Safety endpoints:<br /><br>* Detrimental changes in physical, laboratory or ECG parameters during the<br /><br>study period up to 2 weeks after discontinuation of the study medication.<br /><br>* The occurrence of adverse events (i.e. hospitalization for anginal symptoms<br /><br>and/or myocardial infarction) during the study period up to 2 weeks after<br /><br>discontinuation of the study medication.<br /><br>All possible side effects will be recorded during the study period up to 2<br /><br>weeks after discontinuation of the study medication.</p><br>