Coronary Spasm
Conditions
Keywords
epicardial spasm, endothelin receptor antagonism, angina
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
Interventions
Oral capsules twice daily
OTHERPlacebo control
Oral capsules twice daily
Sponsors
UMC Utrecht
Catharina Ziekenhuis Eindhoven
Maasstad Hospital
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of MACE | 10 weeks | Assessed by (S)AE reporting, during all follow-up contacts |
| Improvement of quality of life | 10 weeks | Measured with EuroQol 5 Dimensions (EQ5D) and separate SAQ domains. Scores can range from 0-100, with higher scores indicating better health status. |
| Microvascular spasm | 10 weeks | The rate of occurence of microvascular spasm according to COVADIS criteria at fuCFT |
| Incidence of liver panel disturbances | 10 weeks | Assessed by means of repeat laboratory analysis |
| Change in spasm provocation reactivity | 10 weeks | Any deterioration or improvement according to prespecified outcomes measured by repeated spasm provocation test. If a higher dose of acetylcholine is needed to induce epicardial spasm for example, this change will be documented. If microvascular spasm can, but epicardial can not be provoked, this will be documented. The incidence of these changes will be analyzed. |
| Rate of study drug discontinuation / study withdrawal. | 10 weeks | Assessed and captured at every follow-up contact moment. |
| Endothelin levels at baseline | 10 weeks | Circulating endothelin-1 plasma levels in peripheral blood drawn at visit 1. |
| Incidence of hypotension | 10 weeks | Assessed by means of repeat blood pressure measurements |
Countries
Netherlands
Outcome results
None listed