Edit-Cmd

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud universitair medisch centrum

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

completed 21 Apr 2026

Decision date (initial)

2024-04-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512030-15-00

EudraCT number

2018-003518-41

ClinicalTrials.gov

NCT04777045

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Our primary objective is to assess the effect of diltiazem on coronary microvascular function as assessed by CFT in symptomatic patients with CMD. Our secondary objective is to assess the effect of diltiazem on the individual coronary function parameters.

Conditions and MedDRA coding

Angina

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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: • 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 4. Baseline coronary function 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

Exclusion criteria 1

1. 1. Other cause of angina deemed highly likely by the treating physician. 2. 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. 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 function testing: a. Contraindication or known hypersensitivity to adenosine. b. Contraindication or known hypersensitivity to acetylcholine. c. Ongoing dipyridamole treatment. 12. 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. 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 within one month prior to enrolment. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients having a successful treatment with diltiazem, defined as normalization of at least one abnormal parameter and none of the normal parameters becoming abnormal. A normal IMR is specified as IMR < 25, a normal CFR being a CFR > 2 and a normal acetylcholine test is specified as one without spasm, without ischemic ECG abnormalities and without (recognizable) angina at the same acetylcholine dose used at baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud universitair medisch centrum

Sponsor organisation

Stichting Radboud universitair medisch centrum

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Tijn Jansen

Public contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Tijn Jansen

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications