Efficacy of Diltiazem to improve coronary microvascular dysfunction: A randomized clinical trial
- Conditions
- Coronary Microvascular DysfunctionMicrovascular angina1001108210003216
- Registration Number
- NL-OMON49283
- Lead Sponsor
- Radboud Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 107
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.
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
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 reactivity 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, and/or 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 during the last 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The proportion of patients having a successful treatment with diltiazem,<br /><br>defined as normalization of at least one abnormal parameter A normal IMR is<br /><br>specified as IMR < 25, a normal CFR being a CFR > 2 and a normal acetylcholine<br /><br>test is specified as one without ECG abnormalities and without signs of spasm<br /><br>at the same acetylcholine dose used at baseline. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Change in the different parameters of the CRT (change in IMR, CFR,<br /><br>acetylcholine test parameters and absolute coronary blood flow). </p><br>