Clinical trial NCT06432452: Efficacy of Endothelin Receptor Antagonism in Coronary Artery Spasm
Official title: Efficacy of Endothelin Receptor Antagonism in Treatment of Coronary Artery Spasm: a Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
PHASE3
Conditions: Coronary Spasm
Keywords: epicardial spasm
endothelin receptor antagonism
angina
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: Catharina Ziekenhuis Eindhoven
name: Maasstad Hospital
First posted: 2024-05-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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).

Primary outcomes:
measure: Successful treatment
timeFrame: 10 weeks
Secondary outcomes:
measure: Improvement of anginal complaints
timeFrame: 10 weeks
Other outcomes:
measure: Improvement of quality of life
timeFrame: 10 weeks
measure: Microvascular spasm
timeFrame: 10 weeks
measure: Endothelin levels at baseline
timeFrame: 10 weeks
measure: Change in spasm provocation reactivity
timeFrame: 10 weeks
measure: Incidence of liver panel disturbances
timeFrame: 10 weeks
measure: Incidence of hypotension
timeFrame: 10 weeks
measure: Incidence of MACE
timeFrame: 10 weeks
measure: Rate of study drug discontinuation / study withdrawal.
timeFrame: 10 weeks
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
state: Noord-Brabant
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
state: Zuid-Holland
city: Nijmegen
country: Netherlands
facility: RadboudUMC
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: Radboud University Medical Center
name: Peter Damman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: