Efficacy of Endothelin Receptor Antagonism in Coronary Artery Spasm

NCT06432452 | Enrolling By Invitation Phase 2

• 1 other identifier: 114746
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

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

Conditions

Coronary Spasm

Keywords

epicardial spasm; endothelin receptor antagonism; angina

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Improvement of anginal complaints

  10 weeks

Other Outcomes (8)

• Improvement of quality of life

  10 weeks

• Microvascular spasm

  10 weeks

• Endothelin levels at baseline

  10 weeks

Study Arms (2)

Bosentan

EXPERIMENTAL

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

Drug: Endothelin Receptor Antagonist

Placebo

PLACEBO COMPARATOR

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

Other: Placebo control

Interventions

Endothelin Receptor Antagonist DRUG

Oral capsules twice daily

Also known as: Bosentan

Bosentan

Placebo control OTHER

Oral capsules twice daily

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• 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)
• Adequate in this case meaning if on hormonal contraceptives, additional measures to be taken (e.g. condom).

Sponsors & Collaborators

• Radboud University Medical Center: lead
• UMC Utrecht: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• Maasstad Hospital: collaborator

Study Sites (4)

Catharina Ziekenhuis

Eindhoven, North Brabant, 5623EJ, Netherlands

Location

Maasstad Hospital

Rotterdam, South Holland, 3079DZ, Netherlands

Location

RadboudUMC

Nijmegen, 6525GA, Netherlands

Location

UMC Utrecht

Utrecht, 3584CX, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 40274007 DERIVED

MeSH Terms

Conditions

Angina Pectoris, Variant; Angina Pectoris

Interventions

Endothelin Receptor Antagonists; Bosentan

Condition Hierarchy (Ancestors)

Angina, Unstable; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Peter Damman, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2024
• First Posted: May 29, 2024
• Study Start: November 11, 2024
• Primary Completion: June 15, 2026
• Study Completion: July 1, 2026
• Last Updated: November 18, 2024

Record last verified: 2024-11

Locations

NL (4)