ALLACS: Allopurinol in Acute Coronary Syndrome

Sponsor

Stephen McSwiggan (Other)

Overall Status

Terminated

CT.gov ID

NCT01457820

Collaborator

British Heart Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Stable Angina	Drug: Allopurinol Drug: Allopurinol Drug: Placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Allopurinol High dose	Drug: Allopurinol Stat dose Allopurinol 800mg, then 400mg BD for 5 days
Experimental: Allopurinol Low dose	Drug: Allopurinol Stat dose Allopurinol 400mg, then 300mg BD for 5 days
Placebo Comparator: Placebo	Drug: Placebo Matched placebo, stat dose, then 5 days of matched placebo BD.

Arm

Intervention/Treatment

Experimental: Allopurinol High dose

Drug: Allopurinol

Stat dose Allopurinol 800mg, then 400mg BD for 5 days

Experimental: Allopurinol Low dose

Drug: Allopurinol

Stat dose Allopurinol 400mg, then 300mg BD for 5 days

Placebo Comparator: Placebo

Drug: Placebo

Matched placebo, stat dose, then 5 days of matched placebo BD.

Outcome Measures

Primary Outcome Measures

Change in time to exercise induced ST depression [4 hours, 1 day and 5 days post study drug testing compared to Baseline 1 hour pre study drug]
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.

Secondary Outcome Measures

change in total exercise time on Exercise Tolerance Testing (ETT) [4 hours, 1 day and 5 days post study drug testing compared to Baseline 1 hour pre study drug]
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.
Change in time to subjects reported symptoms of chest pain during exercise testing. [hours, 1 day and 5 days post study drug testing compared to Baseline 1 hour pre study drug]
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.
changes in blood markers, specifically Brain Naturetic Peptide (BNP), high sensitivity Troponin T and high sensitivity C Reactive Protein (hsCRP), during exercise testing [Pre and post 4 hour ETT compared to baseline]
Baseline is pre 1st study drug dose exercise tolerance test (ETT). Comparisons will be made before and after 4 hour post drug ETT
angina pain and Glyceryl TriNitrate (GTN) usage [Weekly]
subjects will use angina log to record symptoms of angina and GTN usage between hospital visits

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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