BOSENTAN for Coronary vasospasm | Coronary vasomotor dysfunction

Inclusion criteria

• {"criterion_text":"- Definitive diagnosis of epicardial vasospasm on maximal acetylcholine dose of 100µg (at iCFT)\n- At least 18 years of age\n- On optimal regular care ( current or previous treatment with at least 2 daily antianginal medicines i.e. nitrate and calcium channel blocker)\n- Continuing episodes of angina(-like) complaints at least once weekly despite optimal regular care\n- Signed online informed consent for participation in NL-CFT registry, or willing to co-sign for registry at time of inclusion in EDIT-CAS\n- Written informed consent for EDIT-CAS"}

Exclusion criteria

• {"criterion_text":"- Systolic blood pressure (SBP) <85mmHg measured at Visit 1\n- Potentially dangerous interaction due to the use of another CYP3A4 or CYP2C9 substrate (see appendix A: ciclosporin A, glibenclamide, fluconazole, rifampicine, tacrolimus/sirolimus, lopinavir/ritonavir)\n- Repeat spasm provocation test deemed unsafe (e.g. allergic reaction at iCFT)\n- 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)\n- Severe anemia (Hb<6.0mmol/L) without identified cause at time of inclusion\n- Patients with limited life expectancy (<1 year)\n- Participation in another randomized clinical study with an use of an Investigational Medicinal Product (IMP) up to one month prior to enrolment.\n- 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).\n- Known heart failure with reduced ejection fraction<35%\n- Known pulmonary hypertension of any type"}

Primary endpoints

• {"endpoint_text":"- Successful treatment is defined as absence of epicardial vasospasm according to COVADIS criteria (see Table 1 explanatory text in protocol) during repeat spasm provocation test at 10 weeks.","definition_or_measurement_approach":"Assessed at repeat spasm provocation test (fuCFT) at 10 weeks; absence of epicardial vasospasm according to COVADIS criteria defines successful treatment."}

Secondary endpoints

• {"endpoint_text":"- Angina relief. The mean within subject change in SAQSS from baseline to 10 weeks is assessed and compared between bosentan and placebo group.","definition_or_measurement_approach":"Mean within-subject change in Seattle Angina Questionnaire Summary Score (SAQSS) from baseline to 10 weeks compared between treatment arms."}
• {"endpoint_text":"- Explorative: Anginal complaints and quality of life","definition_or_measurement_approach":"Exploratory assessment of anginal complaints and quality of life (e.g. EQ-5D at 10 weeks)."}
• {"endpoint_text":"- Explorative: Microvascular spasm","definition_or_measurement_approach":"Exploratory assessment of presence/change in microvascular spasm on repeat testing."}
• {"endpoint_text":"- Explorative: Endothelin levels","definition_or_measurement_approach":"Exploratory assessment of circulating endothelin levels at baseline and changes thereafter."}
• {"endpoint_text":"- Explorative: Improvement, deterioration or no effect on spasm","definition_or_measurement_approach":"Exploratory classification of change in spasm status (improvement, deterioration, or no effect) on repeat provocation testing."}
• {"endpoint_text":"- Explorative safety endpoint: by means of repeat laboratory analysis, blood pressure measurements and the occurrence of major adverse cardiovascular events (MACE), other adverse events (hospitalization for hypotension, angina or myocardial infarction) and rate and reason of study drug discontinuation / study withdrawal","definition_or_measurement_approach":"Safety assessed by repeated lab analyses, blood pressure measurements, occurrence of MACE, other AEs (hospitalization for hypotension, angina, MI) and rates/reasons for study drug discontinuation/withdrawal."}

Netherlands

Earliest CTIS Part Ii Submission Date

08-04-2024

Latest Decision Or Authorization Date

25-02-2026

Processing Time Days

685

Number Of Sites

5

Number Of Participants

100

Primary sponsor

Full Name

Stichting Radboud University Medical Center

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"Hartstichting","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Abbott","duties_or_roles":"","organisation_type":""}