Diltiazem hydrochloride for Angina | Coronary microvascular dysfunction

Inclusion criteria

• {"criterion_text":"- 1.\tPatients above the age of 18.\n- 2.\tPatients with chronic angina, defined as symptoms of angina at least 2 times a week despite medical therapy for the last 3 months.\n- 3.\tNo signs of obstructive coronary artery disease (CAD), documented within 5 years* before inclusion by one of the following modalities: •\tPatients 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. •\tCoronary computed tomography angiography (CCTA) with finding of non-obstructive coronary arteries\n- 4.\tBaseline coronary function testing with at least one of the following: a.\tCFR ≤ 2.0 b.\tIMR ≥ 25 c.\tAbnormal acetylcholine test defined as the presence of (recognizable) angina, ischemic ECG abnormalities with or without epicardial spasm.\n- 5.\tSigned written informed consent"}

Exclusion criteria

• {"criterion_text":"- 1.\tOther cause of angina deemed highly likely by the treating physician.\n- 2.\tActive 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.\n- 3.\tLeft ventricular ejection fraction < 50%.\n- 4.\tRecent PCI within the past 3 months.\n- 5.\tPatients with history of coronary artery bypass grafting (CABG).\n- 6.\tSurgically uncorrected significant congenital or valvular heart disease, cardiomyopathy or myocarditis.\n- 7.\tSignificant renal impairment (eGFR < 30).\n- 8.\tSignificant hepatic impairment (history or cirrhosis or abnormal serum ALT or AST 3-fold greater than the upper limit of normal).\n- 9.\tPregnant women or women of child bearing potential who are planning to become pregnant within the next 3 months.\n- 10.\tPrior non-cardiac illness with an estimated life expectancy < 1 year.\n- 11.\tContra-indication to coronary function testing: a.\tContraindication or known hypersensitivity to adenosine. b.\tContraindication or known hypersensitivity to acetylcholine. c.\tOngoing dipyridamole treatment.\n- 12.\tContra-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.\n- 13.\tSymptomatic hypotension or systolic BP < 100 mmHg at screening visit on 2 consecutive measurements.\n- 14.\tHistory 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.\n- 15.\tParticipation in another clinical study with an IMP within one month prior to enrolment.\n- 16.\tInability 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.\n- 17.\tUnable to give informed consent (i.e. due to language barrier)."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Proportion of patients meeting the composite success definition based on coronary function testing (CFT) parameters: IMR measured and considered normal if IMR < 25; CFR measured and considered normal if CFR > 2; acetylcholine provocation test evaluated as normal if no spasm, no ischemic ECG abnormalities and no (recognizable) angina at the same acetylcholine dose used at baseline."}

Netherlands

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

04-04-2024

Processing Time Days

2

Number Of Sites

3

Number Of Participants

126

Primary sponsor

Full Name

Stichting Radboud universitair medisch centrum

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands