ReACHallenge Trial: Acetylcholine Rechallenge After Pretreatment With Vasoactive Drugs

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the feasibility and clinical value of acetylcholine (ACH) rechallenge after intracoronary verapamil +- nitroglycerine in a patient cohort with angina and non-obstructive coronary arteries (ANOCA). The main questions it aims to answer are: to determine the efficacy of these drugs in treating ACH-induced coronary artery spasm to determine the efficacy of these drugs in preventing ACH-induced coronary artery spasm The ACH rechallenge will take place during the index coronary function tests in patients with proven ACH-induced vasospastic angina. The study is considered a feasibility study, no control arm is included.

Official Title
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Stepwise Treatment and Acetylcholine Rechallenge in Vasospastic Angina to Guide Patient-tailored Treatment

Conditions
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Angina Pectoris, Variant, Angina Pectoris; Spasm-Induced, Angina Pectoris With Normal Coronary Arteriogram

Intervention / Treatment
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* Diagnostic Test: Acetylcholine rechallenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically indicated coronary angiogram in the setting of angina with non-obstructive coronary artery disease (ANOCA) Non-obstructive coronary artery disease is defined as the absence of coronary artery stenosis ≥ 50%, or if ≥ 50% with non-ischemic resting (RFR > 0.89) and hyperemic indices (FFR > 0.80). ACH provoked epicardial and/or microvascular spasm Left ventricular ejection fraction (LVEF) > 50% Renal function with eGFR ≥ 40 ml/min Exclusion Criteria: Obstructive coronary artery disease (both chronic and acute coronary coronary syndromes) Any cardiomyopathy (including takotsubo stress cardiomyopathy) or severe valvular disease LVEF < 50% Long QT syndrome (LQTS) - genetic or acquired Ventricular paced rhythm Renal failure with eGFR < 40 ml/min Thyroid stimulating hormone (TSH) < lower limit of normal (LLN). A subject taking thyroid replacement therapy may be enrolled with TSH level below LLN if, in the opinion of the investigator, the subject is in a clinically euthyroid state. Known hypersensitivity or contra-indication for either acetylcholine, verapamil, nicorandil or nitroglycerine. Pregnant female subjects. Female subjects of child-bearing potential should be on adequate contraceptive measures or are to be screened with a urine pregnancy test.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vasospastic angina<br>Interventional diagnostic protocol | Diagnostic Test: Acetylcholine rechallenge<br>* STEP 1 consists of verapamil 1mg IC. Angiography after 60 seconds, if spasm persists, NTG 200µg IC is given (step 2). If verapamil suppresses spasm, ACH rechallenge (ACHR) is performed after 3 minutes. In STEP 2, patients with persistent spasm after verapamil or with spasm after ACHR receive NTG 200µg IC. Angiography after 60 seconds, if spasm persists, NTG 200µg IC is delivered again. If refractory spasm occurs, atropine 1mg IV is given. Coronary spasm is considered suppressed once ACHR can no longer provoke spasm. NTG 200µg IC is given as final drug regardless of spasm. ACHR consists of ACH 100 or 200µg IC depending on the dose that previously provoked the coronary artery spasm (both microvascular and epicardial spasm).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of ACH provoked spasm that is no longer inducible by ACH after IC injection of verapamil. | Is verapamil able to suppress ACH-induced coronary artery spasm? | Baseline | 
| The percent of ACH provoked spasm that is no longer inducible by ACH after sequential IC injection of verapamil and NTG. | Is verapamil + NTG able to suppress ACH-induced coronary artery spasm? | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of ACH provoked spasm that resolves after IC administration of verapamil. | How efficient is verapamil IC as a treatment for ACH-induced coronary artery spasm? | Baseline | 
| The percent of ACH provoked spasm that resolves after sequential IC administration of verapamil and NTG. | How efficient is verapamil and NTG IC as a treatment for ACH-induced coronary artery spasm? | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vasospastic angina, Angina with non-obstructive coronary arteries (ANOCA), Acetylcholine