ReACHallenge Trial: Acetylcholine Rechallenge After Pretreatment With Vasoactive Drugs

NCT05618132 | Unknown

• 1 other identifier: 2806
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Vasospastic angina; Angina with non-obstructive coronary arteries (ANOCA); Acetylcholine

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• The percent of ACH provoked spasm that resolves after IC administration of verapamil.

  Baseline

• The percent of ACH provoked spasm that resolves after sequential IC administration of verapamil and NTG.

  Baseline

Other Outcomes (3)

• Proportion of patients with epicardial coronary artery spasm who have microvascular spasm after either verapamil or verapamil + NTG.

  Baseline

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  Baseline

• Absolute changes in the individual, overall and summary score of the Seattle Angina Questionnaire (SAQ) from baseline to the first ambulatory control visit.

  Baseline, 1 month

Study Arms (1)

Vasospastic angina

EXPERIMENTAL

Interventional diagnostic protocol

Diagnostic Test: Acetylcholine rechallenge

Interventions

Acetylcholine rechallenge DIAGNOSTIC_TEST

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).

Vasospastic angina

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Antwerp: lead

Study Sites (1)

University Hospital Antwerp

Antwerp, 2650, Belgium

RECRUITING

MeSH Terms

Conditions

Angina Pectoris, Variant; Angina Pectoris; Microvascular Angina

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

Study Officials

• Tijs Bringmans

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tijs Bringmans

CONTACT

+32 3 821 3843; tijs.bringmans@uza.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 16, 2022
• Study Start: January 9, 2023
• Primary Completion: January 1, 2024
• Study Completion: June 1, 2024
• Last Updated: January 19, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)