ReACHallenge Trial: Acetylcholine Rechallenge After Pretreatment With Vasoactive Drugs (ReACHallenge)

January 17, 2023 updated by: University Hospital, Antwerp

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Antwerp, Belgium, 2650
        • Recruiting
        • University Hospital Antwerp
        • Contact:
        • Sub-Investigator:
          • Vincent FM Segers

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vasospastic angina
Interventional diagnostic protocol
Diagnostic test: Acetylcholine rechallenge

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).

What is the study measuring?

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.
Time Frame: Baseline
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.
Time Frame: Baseline
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.
Time Frame: Baseline
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.
Time Frame: Baseline
How efficient is verapamil and NTG IC as a treatment for ACH-induced coronary artery spasm?
Baseline

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with epicardial coronary artery spasm who have microvascular spasm after either verapamil or verapamil + NTG.
Time Frame: Baseline
Do microvascular and epicardial vasospasm occur simultaneously and is it possible to unmask microvascular spasm with either verapamil or verapamil + NTG.
Baseline
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time Frame: Baseline
Are there safety concerns related to the proposed ACH rechallenge protocol?
Baseline
Absolute changes in the individual, overall and summary score of the Seattle Angina Questionnaire (SAQ) from baseline to the first ambulatory control visit.
Time Frame: Baseline, 1 month
Does treatment based on the current protocol improve control of angina at the first ambulatory visit compared to before the coronary function tests?
Baseline, 1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Antwerp

Investigators

  • Principal Investigator: Tijs Bringmans, University Hospital, Antwerp

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 9, 2023

Primary Completion (Anticipated)

January 1, 2024

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

November 8, 2022

First Submitted That Met QC Criteria

November 8, 2022

First Posted (Actual)

November 16, 2022

Study Record Updates

Last Update Posted (Actual)

January 19, 2023

Last Update Submitted That Met QC Criteria

January 17, 2023

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2806

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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