Effect of Diltiazem to improve the function of the coronary arteries

Phase 1

• Conditions: Coronary Microvascular Dysfunction (CMD). In CMD, ischemia is caused by impaired endothelial and/or non-endothelial coronary vasoreactivity resulting in the coronary microvasculature not dilating properly or becoming vasospastic.; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

• Registration Number: EUCTR2018-003518-41-NL
• Lead Sponsor: Radboudumc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-26
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 142

Inclusion Criteria

1.Patients above the age of 18.
2.Patients with chronic angina, defined as symptoms of angina at least 2 times a week despite medical therapy for the last 3 months.
3.No signs of obstructive coronary artery disease (CAD), documented within 5 years* before inclusion by one of the following modalities:
a.Coronary angiography: patients with non-obstructive (<50% stenosis) coronary arteries are eligible, or patients with intermediate stenosis (between 50 and 70%) with documented FFR >0.80 or iFR >0.89 on angiogram. In patients with a history of stenting are eligible if they have no current significant coronary epicardial stenoses, a minimum diameter stenosis of <10% is required.
b.Coronary computed tomography angiography (CCTA) with finding of non-obstructive coronary arteries
4.Baseline coronary reactivity testing with at least one of the following:
a.CFR = 2.0
b.IMR = 25
c.Abnormal acetylcholine test defined as the presence of (recognizable) angina, ischemic ECG abnormalities with or without epicardial spasm
5.Signed written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

Exclusion Criteria

1.Other cause of angina deemed highly likely by the treating physician.
2.Active use of non-dihydropyridine calcium channel blockers or any use of non-dihydropyridine calcium channel blockers in the previous month or known intolerance for non-dihydropyridine calcium channel blockers.
3.Left ventricular ejection fraction < 50%.
4.Recent PCI within the past 3 months.
5.Patients with history of coronary artery bypass grafting (CABG).
6.Surgically uncorrected significant congenital or valvular heart disease, cardiomyopathy or myocarditis.
7.Significant renal impairment (eGFR < 30).
8.Significant hepatic impairment (history or cirrhosis or abnormal serum ALT or AST 3-fold greater than the upper limit of normal).
9.Pregnant women or women of child bearing potential who are planning to become pregnant within the next 3 months.
10.Prior non-cardiac illness with an estimated life expectancy < 1 year.
11.Contra-indication to coronary reactivity testing:
a.Contraindication or known hypersensitivity to adenosine.
b.Contraindication or known hypersensitivity to acetylcholine.
c.Contraindication to aminophylline.
d.Ongoing dipyridamole treatment.
12.Contra-indication for treatment with CCB: second or third degree AV block, sinus node dysfunction and/or bradycardia (heart rate < 40 beats/minute)
13.Symptomatic hypotension or systolic BP < 100 mmHg at screening visit on 2 consecutive measurements.
14.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.
15.Participation in another clinical study with an IMP during the lastwithin one month prior to enrollment.
16.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.
17.Unable to give informed consent (i.e. due to language barrier).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified