Evaluation of Diltiazem Hydrochloride on Coronary Microvascular Dysfunction in Symptomatic Angina Patients: A Randomized Controlled Trial
- Trial ID
- 2024-512030-15-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **diltiazem** on coronary microvascular function in symptomatic patients with coronary microvascular dysfunction (CMD), as assessed by coronary flow reserve testing (CFT). This is clinically relevant as CMD is a condition that can lead to **angina** and other cardiovascular complications, and improving microvascular function could potentially alleviate symptoms and improve patient outcomes.
Participants
The clinical trial involves participants diagnosed with **angina**, specifically targeting individuals with chronic symptoms occurring at least twice a week despite ongoing medical therapy. The study population includes both male and female subjects, aged 18 years and older, with no signs of obstructive coronary artery disease as documented by specific diagnostic criteria. The trial does not include a vulnerable population. Participants were selected based on their coronary microvascular function, with baseline testing indicating specific coronary function parameters. The sponsor has not provided the total number of participants involved in the study. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** of **diltiazem hydrochloride** in improving coronary microvascular dysfunction in patients with chronic **angina**. This study is a randomized, double-blind, controlled trial, with a placebo group receiving **microcrystalline cellulose**. The trial is expected to last until May 2026, with participant recruitment having commenced in November 2019. The trial involves a series of structured visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, symptoms, and coronary artery status. Participants must be over 18 years old, have chronic angina, and show no signs of obstructive coronary artery disease.
Following the screening, eligible participants will be randomized to receive either the active treatment or placebo. The trial includes regular follow-up visits to monitor the participants' response to the treatment and to assess coronary function parameters. The primary endpoint is the proportion of patients achieving successful treatment, defined by the normalization of at least one abnormal coronary function parameter without any normal parameters becoming abnormal. The study will conclude with an end-of-study visit to evaluate the overall treatment outcomes and gather final data.
Participant involvement is expected to last up to six months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include adverse reactions to the treatment, withdrawal of consent, or any significant protocol deviations. The trial's methodology ensures rigorous data collection and analysis to determine the therapeutic potential of diltiazem in this patient population.
Treatment
The clinical trial involves the administration of two treatments. The first treatment is **microcrystalline cellulose**, which serves as a placebo in this study. It is provided in the form of an **oral powder**. The maximum daily dose is 360 mg, and the administration route is oral. The treatment period is set for a maximum of 6 months. The microcrystalline cellulose is a polymer-based substance, and its role in the trial is to act as a control to compare against the active treatment.
The second treatment is **Diltiazem HCl Auro retard 120 mg**, which is the experimental medication being tested for its efficacy in improving coronary microvascular dysfunction. This medication is provided as a **modified-release tablet**. The active substance, **diltiazem hydrochloride**, is a chemical compound. The maximum daily dose is also 360 mg, administered orally. The treatment duration is up to 6 months. The modified-release formulation is designed to ensure a controlled release of the active substance over time, enhancing its therapeutic effect. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.
Efficacy
The efficacy of diltiazem in improving coronary microvascular dysfunction will be assessed in this randomized clinical trial. The primary endpoint is the proportion of patients achieving successful treatment with diltiazem, defined by the normalization of at least one abnormal coronary function parameter without any normal parameters becoming abnormal. The parameters include the **Index of Microcirculatory Resistance (IMR)**, with a normal value specified as IMR < 25, the **Coronary Flow Reserve (CFR)**, with a normal value being CFR > 2, and the acetylcholine test, which is considered normal if there is no spasm, no ischemic ECG abnormalities, and no recognizable angina at the same acetylcholine dose used at baseline.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Recruiting | 25 Nov 2019 | — |
| Netherlands | — | — | 126 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CELLULOSE, MICROCRYSTALLINE | Placebo | — | ORAL | 360 | 6 | SUB12626MIG |
Diltiazem HCl Auro retard 120 mg, tabletten met gereguleerde afgifte | Test | TABLETTEN MET GEREGULEERDE AFGIFTE | ORAL | 360 | 6 | PRD663820 |