Efficacy and Safety of Lacidipine in Chronic Stable Angina

Study Overview
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Brief Summary
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The aim of this study was to explore whether lacidipine at doses of 2 mg, 4 mg and 6 mg decreased the symptoms of angina, compared to placebo in patients with chronic stable angina

Official Title
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A Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel Group, Dose Ranging Study to Investigate the Efficacy and Safety of Lacidipine in Chronic Stable Angina.

Conditions
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Angina Pectoris

Intervention / Treatment
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* Drug: Lacidipine, low dose
* Drug: Lacidipine, medium dose
* Drug: Lacidipine, high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 80 years History of stable, exertional angina pectoris (Canadian Cardiovascular Society functional class II to III) for at least 3 months duration prior to enrolment in the study Patients not currently receiving treatment with antianginal medication (other than short-acting nitrates) Between visits 2 and 3 two treadmill exercise tests, demonstrating ≥ 0.1 mV of horizontal or down sloping ST-segment depression, must be carried out. The difference in symptom-limited exercise duration between these two tests must not exceed 20% Total treadmill exercise duration > 3 minutes (i.e. stage 2 or above on a standard Bruce protocol) Coronary artery disease, preferably (not mandatory) documented by a history of proven myocardial infarction and/or coronary angiography indicating ≥ 50% reduction in luminal diameter of one or more coronary arteries or their primary branches Exclusion Criteria: Myocardial infarction within 3 months prior to enrolment in the study Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery within 6 months Other types of angina (variant, unstable) Uncontrolled hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg) Resting heart rate < 50 bpm or > 100 bpm Significant valvular heart disease Heart failure New York Heart Association Class III or IV Chronic obstructive pulmonary disease and/or asthma with clinical symptoms requiring regular medication Significant arrhythmia (since this may interfere with the interpretation of the electrocardiogram) including Wolff Parkinson-White syndrome, atrial fibrillation, atrial flutter, sick sinus syndrome, significant Atrio-Ventricular heart block, intraventricular conduction defect (QRS > 0.12 seconds) ventricular pre-excitation, bundle branch block, the presence of a pace-maker, the presence of an implanted automatic defibrillator, uncorrected hypokalaemia (potassium < 3.5 mmol/litre) Insulin dependent diabetes mellitus Significant liver disease (Aspartate Aminotransferase or Alanine Aminotransferase > twice the upper limit of reference range) Significant renal disease (creatinine > 1.5 x upper limit of reference range) Any clinical condition which in the opinion of the investigator, would preclude the safe fulfilment of the protocol and the safe administration of trial medication Inability to perform repeated exercise testing due to extra-cardiac reasons Concomitant treatment with any other anti-anginal medication, whether or not prescribed for this indication (e.g. calcium channel blockers, β-blockers or long-acting nitrates) Concomitant treatment with anti-arrhythmic medication, digitalis or tricyclic anti-depressants or other agents known to affect ST-segment morphology Known hypersensitivity to any of the components of the investigational drug Pregnant or nursing women or women of child bearing potential Participation in any other clinical trial within 2 months of enrolment History of drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lacidipine, low dose<br> | Drug: Lacidipine, low dose<br> <br> Drug: Placebo<br> <br> |
| Experimental: Lacidipine, medium dose<br> | Drug: Lacidipine, medium dose<br> <br> Drug: Placebo<br> <br> |
| Experimental: Lacidipine, high dose<br> | Drug: Lacidipine, high dose<br> <br> |
| Active Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total treadmill exercise duration |  | Baseline, week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in time to ST segment depression (≥ 0.1 mV) |  | up to 6 weeks | 
| Treadmill exercise time to first report of anginal pain |  | week 6 | 
| Reason for termination of treadmill exercise test |  | up to 6 weeks | 
| Frequency/severity of anginal attacks |  | up to 6 weeks | 
| Consumption of short-acting nitrates |  | up to 6 weeks | 
| Number of patients with adverse events |  | up to 6 weeks |