Status:

ACTIVE_NOT_RECRUITING

Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: a Randomized Clinical Trial

Lead Sponsor:

Radboud University Medical Center

Conditions:

Microvascular Angina

Coronary Vasospasm

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

Rationale: Up to 40% of patients undergoing a coronary angiogram for symptoms/signs of ischemia do not have obstructive coronary artery disease (CAD). In about half of them the mechanism underlying ca...

Detailed Description

Primary Objective: To assess the effect of diltiazem on coronary microvascular function in patients with chronic angina and evidence of coronary microvascular dysfunction. Secondary Objectives: To ...

Eligibility Criteria

Inclusion

  • Patients with chronic angina, defined as symptoms of angina at least 2 times a week despite medical therapy for the last 3 months.
  • No signs of obstructive coronary artery disease (CAD), documented within 5 years\* before inclusion by one of the following modalities:
  • Patients with non-obstructive (\< 50% stenosis) coronary arteries, or patients with one or more intermediate stenoses (between 50 and 70%) with documented FFR \> 0.80 or iFR \> 0.89 on angiogram.
  • Coronary computed tomography angiography (CCTA) with finding of non-obstructive coronary arteries
  • Baseline coronary function testing with at least one of the following:
  • CFR ≤ 2.0
  • IMR ≥ 25
  • Abnormal acetylcholine test defined as the presence of (recognizable) angina, ischemic ECG abnormalities with or without epicardial spasm.
  • Signed written informed consent \* Note: in cases of clinically suspected progression of atherosclerosis as per the Investigator, more contemporary (i.e., 6 months) evidence should be provided.

Exclusion

  • Other cause of angina deemed highly likely by the treating physician.
  • Active use of calcium channel blockers or any use of calcium channel blockers in the previous two weeks or known intolerance for non-dihydropyridine calcium channel blockers.
  • Left ventricular ejection fraction \< 50%.
  • Recent PCI within the past 3 months.
  • Patients with history of coronary artery bypass grafting (CABG).
  • Surgically uncorrected significant congenital or valvular heart disease, cardiomyopathy or myocarditis.
  • Significant renal impairment (eGFR \< 30).
  • Significant hepatic impairment (history or cirrhosis or abnormal serum ALT or AST 3-fold greater than the upper limit of normal).
  • Pregnant women or women of child bearing potential who are planning to become pregnant within the next 3 months.
  • Prior non-cardiac illness with an estimated life expectancy \< 1 year.
  • Contra-indication to coronary function testing:
  • Contraindication or known hypersensitivity to adenosine.
  • Contraindication or known hypersensitivity to acetylcholine.
  • Ongoing dipyridamole treatment.
  • Contra-indication for treatment with CCB: second or third degree AV block, sinus node dysfunction, bradycardia (heart rate \< 50 beats/minute) and/or potentially dangerous interaction due to the use of another CYP3A4 substrate in the opinion of the investigator.
  • Symptomatic hypotension or systolic BP \< 100 mmHg at screening visit on 2 consecutive measurements.
  • History of hospitalization for asthma and/or current use of ≥ 2 types of pulmonary medications for asthma and/or severe COPD with FEV1 \< 50% of predicted.
  • Participation in another clinical study with an IMP within one month prior to enrolment.
  • Inability of the patient, in the opinion of the investigator, to understand and/or comply with study medications, procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study.
  • Unable to give informed consent (i.e. due to language barrier).

Key Trial Info

Start Date :

October 25 2019

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 1 2026

Estimated Enrollment :

85 Patients enrolled

Trial Details

Trial ID

NCT04777045

Start Date

October 25 2019

End Date

December 1 2026

Last Update

March 30 2023

Active Locations (3)

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Page 1 of 1 (3 locations)

1

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands, 6525 GA

2

Catharina Hospital

Eindhoven, Netherlands

3

Maasstad Hospital

Rotterdam, Netherlands

Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: a Randomized Clinical Trial | DecenTrialz