Allopurinol in Acute Coronary Syndrome

Study Overview
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Brief Summary
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Allopurinol is a drug commonly used to treat gout. However recent studies have shown it has the potential to help improve oxygen supply to heart muscle. In this study the Investigators aim to find out if allopurinol slows down the onset of angina symptoms, as seen by a doctor on a tracing of the heart (ECG- electrocardiogram), for patients who have been diagnosed with heart disease, when exercising on a treadmill. The Investigators are also are trying to figure out the best dose of allopurinol to use and to see how quickly it begins working. To do this the investigators will recruit patients with angina, exercise them on a treadmill after giving different doses of allopurinol and see if there is an improvement in their time to bring on angina symptoms and signs. Patients recruited to this trial will receive three different treatment regimes over a six week period. Each treatment regime will last for one week with a one week rest period between each regime. This will involve up to eleven visits to Ninewells Medical School, Dundee for testing.

Official Title
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Allopurinol as a Possible New Therapy for Acute Coronary Syndromes:The Next Steps

Conditions
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Chronic Stable Angina

Intervention / Treatment
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* Drug: Allopurinol
* Drug: Allopurinol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: angiographically documented coronary artery disease, a positive exercise tolerance test (ETT) a history of symptoms of chronic, stable, effort-induced angina for ≥ 2 months. All concomitant antianginal medication will be allowed and continued unchanged during the study. Exclusion Criteria: the inability to do an ETT due to back or leg problems, myocardial infarction or acute coronary syndrome ≤ 2 months, coronary revascularization (percutaneous or CABG) ≤ 6 months, Left Ventricular Ejection Fraction <45%, estimated GFR <60 ml/min or creatinine >180 mmol/ml, significant valvular pathology, already had gout or on allopurinol, atrial arrhythmias or ECG abnormalities interfering with ST-segment interpretation, previous ventricular arrhythmias on ETT, severe hepatic disease or on azathioprine, 6 mercaptopurine or warfarin. Patients who have participated in any other clinical trial within the previous 30 days will be excluded. Patients who are unable to give informed consent will also be excluded from this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allopurinol High dose<br> | Drug: Allopurinol<br>* Stat dose Allopurinol 800mg, then 400mg BD for 5 days<br>|
| Experimental: Allopurinol Low dose<br> | Drug: Allopurinol<br>* Stat dose Allopurinol 400mg, then 300mg BD for 5 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matched placebo, stat dose, then 5 days of matched placebo BD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in time to exercise induced ST depression | A continuous ECG tracing will be recorded. Time to >1mm change in ST measurements will be noted. Exercise Tolerance testing (ETT) 1 hour before study drug administration is baseline measurement. Comparisons will be made 4 hours, 1 day and 5 days after baseline ETT. | 4 hours, 1 day and 5 days post study drug testing compared to Baseline 1 hour pre study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in total exercise time on Exercise Tolerance Testing (ETT) | A continuous ECG tracing will be recorded. Time to total exercise time, ie when patient can walk no further will be noted. Exercise Tolerance Testing (ETT) 1 hour before study drug administration is baseline measurement. Comparisons will be made 4 hours, 1 day and 5 days after baseline ETT. | 4 hours, 1 day and 5 days post study drug testing compared to Baseline 1 hour pre study drug | 
| Change in time to subjects reported symptoms of chest pain during exercise testing. | A continuous ECG tracing will be recorded. Time to reported chest pain will be noted. Exercise Tolerance testing (ETT) 1 hour before study drug administration is baseline measurement. Comparisons will be made 4 hours, 1 day and 5 days after baseline ETT. | hours, 1 day and 5 days post study drug testing compared to Baseline 1 hour pre study drug | 
| changes in blood markers, specifically Brain Naturetic Peptide (BNP), high sensitivity Troponin T and high sensitivity C Reactive Protein (hsCRP), during exercise testing | Baseline is pre 1st study drug dose exercise tolerance test (ETT). Comparisons will be made before and after 4 hour post drug ETT | Pre and post 4 hour ETT compared to baseline | 
| angina pain and Glyceryl TriNitrate (GTN) usage | subjects will use angina log to record symptoms of angina and GTN usage between hospital visits | Weekly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allopurinol, Angina, Acute coronary syndrome