Coronary SpasmPhase 2/3EDIT-CASNCT06432452
Efficacy of Endothelin Receptor Antagonism in Coronary Artery Spasm
A Phase 2/3 study testing Endothelin Receptor Antagonist in people with Coronary Spasm, run by Radboud University Medical Center at 4 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Spasm
- What is being tested?
- Endothelin Receptor Antagonist
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 4 sitesNetherlands
- Study dates
- 11 Nov 2024to 1 Jul 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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
- Written informed consent for EDIT-CAS
Who cannot join
- 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).
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- 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).
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands4 sites
Catharina Ziekenhuis
Eindhoven, North Brabant, 5623EJ
RadboudUMC
Nijmegen, 6525GA
Maasstad Hospital
Rotterdam, South Holland, 3079DZ
UMC Utrecht
Utrecht, 3584CX
About this study
Official title: Efficacy of Endothelin Receptor Antagonism in Treatment of Coronary Artery Spasm: a Randomized Controlled Clinical Trial
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
- Being tested
- Endothelin Receptor Antagonist, Placebo control
- Keywords
- epicardial spasm, endothelin receptor antagonism, angina
- Medical subject headings
- Angina Pectoris, Variant, Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endothelin Receptor AntagonistDrug
Also called Bosentan
Oral capsules twice daily
Placebo controlOther
Also called Placebo
Oral capsules twice daily
| Study group | Role | What they receive |
|---|---|---|
| Bosentan | Experimental | Bosentan 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks Receives: 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 Receives: Other: Placebo control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10 weeks
Secondary outcomes (1)
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.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2024
- Study start11 Nov 2024
- Primary completion15 Jun 2026 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary SpasmStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht, Catharina Ziekenhuis Eindhoven, Maasstad Hospital
- Responsible party
- Sponsor
- Investigators
- Peter Damman, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06432452
- Sponsor's protocol ID
- 114746
- Acronym
- EDIT-CAS
- Status last verified
- Nov 2024
- First submitted
- 10 May 2024
- Last updated
- 18 Nov 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40274007
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Endothelin Receptor Antagonism in Treatment of Coronary Artery Spasm: a Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT06432452
- Acronym / sponsor ID
- EDIT-CAS / 114746
- Conditions
- Coronary Spasm
- Keywords
- epicardial spasm, endothelin receptor antagonism, angina
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- UMC Utrecht, Catharina Ziekenhuis Eindhoven, Maasstad Hospital
- Study start
- 11 Nov 2024 (actual)
- Primary completion
- 15 Jun 2026 (estimated)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 29 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bosentan | Experimental | Drug: Endothelin Receptor AntagonistBosentan 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks |
| Placebo | Placebo comparator | Other: Placebo controlPlacebo 62.5 mg twice daily Uptitrated to 125mg twice daily if tolerated after 4 weeks Total 10 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endothelin Receptor AntagonistAlso: BosentanOral capsules twice daily | Drug | Bosentan |
| Placebo controlAlso: PlaceboOral capsules twice daily | Other | Placebo |
Primary outcome
Successful treatment
Time frame: 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.
1 secondary outcome
Improvement of anginal complaints
Time frame: 10 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2024.
- Derived from this study: PubMed 40274007Crooijmans 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peter Damman, MD, PhD principal investigator
Radboud University Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Endothelin Receptor Antagonist in people with Coronary Spasm, run by Radboud University Medical Center at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Successful treatment (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06432452, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.