Efficacy of Endothelin Receptor Antagonism in Coronary Artery Spasm (EDIT-CAS)

Radboud University Medical Center

Status and phase: Invitation-only; Phase 3; Phase 2

Conditions: Coronary Spasm

Treatments: Other: Placebo control; Drug: Endothelin Receptor Antagonist

Study type: Interventional

Funder types: Other

Identifiers

NCT06432452

114746

Details and patient eligibility

About

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

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups, including a placebo group

Bosentan

Experimental group

Description:

Bosentan 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks

Treatment:

Drug: Endothelin Receptor Antagonist

Placebo

Placebo Comparator group

Description:

Placebo 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks

Treatment:

Other: Placebo control