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| Name | Class |
|---|---|
| UMC Utrecht | OTHER |
| Catharina Ziekenhuis Eindhoven | OTHER |
| Maasstad Hospital | OTHER |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bosentan | Experimental | Bosentan 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks |
|
| Placebo | Placebo Comparator | Placebo 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Endothelin Receptor Antagonist | Drug | Oral capsules twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Successful treatment | 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. | 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement of anginal complaints | As measured with Seattle Angina Questionnaire (SAQ) summary score and change from baseline to follow-up. Score can range from 0-100, with higher scores indicating better health status. | 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement of quality of life | Measured with EuroQol 5 Dimensions (EQ5D) and separate SAQ domains. Scores can range from 0-100, with higher scores indicating better health status. | 10 weeks |
| Microvascular spasm |
Inclusion Criteria:
Exclusion Criteria:
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)
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| Name | Affiliation | Role |
|---|---|---|
| Peter Damman, MD, PhD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Catharina Ziekenhuis | Eindhoven | North Brabant | 5623EJ | Netherlands | ||
| Maasstad Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40274007 | Derived | Crooijmans C, Jansen T, van de Hoef T, Paradies V, de Vos A, Yosofi B, Cetinyurek-Yavuz A, den Ruijter H, Beijk M, Meuwissen M, van Royen N, Elias-Smale S, Dimitriu-Leen A, Damman P; for NL-CFT. Design and rationale of the efficacy of endothelin receptor antagonism in treatment of coronary artery spasm: a randomized controlled trial (EDIT-CAS). Am Heart J. 2025 Oct;288:140-148. doi: 10.1016/j.ahj.2025.04.022. Epub 2025 Apr 22. |
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| ID | Term |
|---|---|
| D000788 | Angina Pectoris, Variant |
| D000787 | Angina Pectoris |
| ID | Term |
|---|---|
| D000789 | Angina, Unstable |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D065128 | Endothelin Receptor Antagonists |
| D000077300 | Bosentan |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000096926 | Benzenesulfonamides |
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| Placebo control | Other | Oral capsules twice daily |
|
|
The rate of occurence of microvascular spasm according to COVADIS criteria at fuCFT
| 10 weeks |
| Endothelin levels at baseline | Circulating endothelin-1 plasma levels in peripheral blood drawn at visit 1. | 10 weeks |
| Change in spasm provocation reactivity | Any deterioration or improvement according to prespecified outcomes measured by repeated spasm provocation test. If a higher dose of acetylcholine is needed to induce epicardial spasm for example, this change will be documented. If microvascular spasm can, but epicardial can not be provoked, this will be documented. The incidence of these changes will be analyzed. | 10 weeks |
| Incidence of liver panel disturbances | Assessed by means of repeat laboratory analysis | 10 weeks |
| Incidence of hypotension | Assessed by means of repeat blood pressure measurements | 10 weeks |
| Incidence of MACE | Assessed by (S)AE reporting, during all follow-up contacts | 10 weeks |
| Rate of study drug discontinuation / study withdrawal. | Assessed and captured at every follow-up contact moment. | 10 weeks |
| Rotterdam |
| South Holland |
| 3079DZ |
| Netherlands |
| RadboudUMC | Nijmegen | 6525GA | Netherlands |
| UMC Utrecht | Utrecht | 3584CX | Netherlands |
| D014652 |
| Vascular Diseases |
| D002637 | Chest Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |