Efficacy of Endothelin Receptor Antagonism in Coronary Artery Spasm

Phase 2

• Conditions: Coronary Spasm
• Interventions: Drug: Endothelin Receptor Antagonist; Other: Placebo control

• Registration Number: NCT06432452
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-10
• Study First Submitted QC: 2024-05-21
• Study First Posted: 2024-05-29
• Status Verified: 2024-11
• Study Start: 2024-11-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18
• Primary Completion: 2026-06-15
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Definitive diagnosis of epicardial vasospasm on maximal acetylcholine dose of 100µg (at iCFT)
2. At least 18 years of age
3. On optimal regular care ( current or previous treatment with at least 2 daily anti-anginal medicines i.e. nitrate and calcium channel blocker
4. Continuing episodes of angina(-like) complaints at least once weekly despite 3.
5. 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
6. Written informed consent for EDIT-CAS

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Exclusion Criteria

1. Systolic blood pressure (SBP) <85 mmHg measured at Visit 1

2. 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)

3. Severe anemia (Hb<6.0mmol/L) without identified cause at time of inclusion

4. Patients with limited life expectancy (<1 year)

5. Participation in another randomized clinical study with an use of an Investigational Medicinal Product (IMP) up to one month prior to enrolment.

6. 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).

7. Known heart failure with reduced ejection fraction<35%

8. Known pulmonary hypertension of any type

9. Potentially dangerous interaction due to the use of another CYP3A4 or CYP2C9 substrate (e.g. ciclosporin A, glibenclamide, fluconazole, rifampicin, tacrolimus/sirolimus, lopinavir/ritonavir)

10. 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bosentan	Endothelin Receptor Antagonist	Bosentan 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks
Placebo	Placebo control	Placebo 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks

Primary Outcome Measures

Name	Time	Method
Successful treatment	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.

Secondary Outcome Measures

Name	Time	Method
Improvement of anginal complaints	10 weeks	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.

Trial Locations

Locations (4)

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Noord-Brabant, Netherlands

Maasstad Hospital; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands

RadboudUMC; 🇳🇱 Nijmegen, Netherlands

UMC Utrecht; 🇳🇱 Utrecht, Netherlands