The Effect of Allopurinol on the Risk of Cardiovascular Events in Patients with Cardiovascular Risk

Phase 3

Recruiting

• Conditions: Cardiovascular Diseases; Uric Acid
• Interventions: Drug: Allopurinol 200 mg; Drug: Optional intervention

• Registration Number: NCT05943821
• Lead Sponsor: Poznan University of Medical Sciences

Brief Summary

Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The ALL-VASCOR study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk, excluding ischemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of death.

Detailed Description

The ALL-VASCOR study is a randomized, double-blind, placebo-controlled, multi-center trial that examines the effect of allopurinol therapy (200-500mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1,116 patients aged 40-70, with serum uric acid levels above 5mg/dL and with high and very high risk for cardiovascular disease. The ALL-VASCOR study is further designed to assess the occurrence of long-COVID syndrome. The study is directed toward both primary and secondary as well as additional endpoints. Due to the duration of the study, the planned intervention will end on July 31,2028, unless the Safe Monitoring Board or other applicable authorities decide about it. Participant recruitment for the ALL-VASCOR study is set to begin in August of 2023 and will be conducted only within Poland.

Study Timeline

• Study First Submitted: 2023-07-05
• Study First Submitted QC: 2023-07-05
• Study First Posted: 2023-07-13
• Study Start: 2023-09-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-03
• Last Update Posted: 2025-01-06
• Primary Completion: 2028-07-31
• Study Completion: 2028-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1116

Inclusion Criteria

1. Age: between 40-70 years old.

2. Giving informed consent to participate in the study.

3. Serum UA levels above 5 mg/dl within the last six months before the screening visit.

4. Meeting at least one of the criteria defining high or very high CV risk includes:

   1. calculated 10-year cardiovascular mortality risk based on SCORE2 >2.5% for patients under 50 years old or ≥5% for patients 50 years old or older

   2. documented occurrence of CV diseases (cerebrovascular disease: ischemic stroke, intracerebral bleeding, TIA; heart failure regardless of the etiology NYHA I - II (without IHD), PAD, atrial fibrillation (de novo or ever)

   3. diabetes or arterial hypertension complicated by organ damage:

      • increase in vascular stiffness: pulse pressure ≥ 60 mmHg, and/or cervicofemoral PWV > 10 m/s;
      • features of left ventricular hypertrophy on echocardiography or electrocardiography;
      • increased urine albumin-creatinine ratio (30-300 mg/g);
      • ankle-brachial index < 0.9.

Exclusion Criteria

1. Taking allopurinol, febuxostat or other hypouricemic drugs.
2. Contraindications to taking allopurinol.
3. Pregnant women, breastfeeding or planning pregnancy during the duration of the study.
4. Hormonal therapy containing oestrogens.
5. Active cancer process or disease in the last five years, excluding locally malignant tumours.
6. Uncontrolled hypertension (mean value ≥ 180/110 mmHg seven days before screening visit) in home measurements despite using hypotensive drugs.
7. 7. Renal insufficiency with an eGFR <45 ml/ min/1.73m2 (according to 2009 CKD-EPI recommendations: stage G3b, G4 and G5).
8. Hypothyroidism or hyperthyroidism not in a state of euthyroidism.
9. Confirmed coronary artery disease (defined as prior AMI, revascularization of the myocardium, confirmed presence of atherosclerotic plaques in coronary arteries on imaging studies).
10. Heart failure in NYHA class III and IV.
11. Taking preparations: azathioprine, mercaptopurine or cyclosporin. Participation in another clinical trial of a medicinal product or medical device within the last three months or five half-lives, whichever period is longer.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Allopurinol 200 mg	The patients will receive placebo at an initial daily dose of 200 mg. The dose may be increased by another 100 mg at visit 3 and by another 100 mg at the visit 4 (up to 500 mg during V4).
Allopurinol	Allopurinol 200 mg	The patients will receive allopurinol at an initial daily dose of 200 mg. If insufficient therapy efficacy is noted, the initial allopurinol dose will be increased by 100 mg (up to 300 mg during V2). Similarly, the dose may be increased by another 100 mg at visit 3 and by another 100 mg at the visit 4 (up to 500 mg during V4).
Allopurinol	Optional intervention	The patients will receive allopurinol at an initial daily dose of 200 mg. If insufficient therapy efficacy is noted, the initial allopurinol dose will be increased by 100 mg (up to 300 mg during V2). Similarly, the dose may be increased by another 100 mg at visit 3 and by another 100 mg at the visit 4 (up to 500 mg during V4).
Placebo	Optional intervention	The patients will receive placebo at an initial daily dose of 200 mg. The dose may be increased by another 100 mg at visit 3 and by another 100 mg at the visit 4 (up to 500 mg during V4).

Primary Outcome Measures

Name	Time	Method
The occurrence of a major adverse cardiovascular event (MACE)	Baseline up to approximately 5 years	The number of all causes of death, cardiac death, stroke, transient ischemic attack, acute coronary syndrome, coronary angioplasty or revascularization, peripheral arterial angioplasty, hospitalization for unstable angina or worsening heart failure

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants of all-cause death	Baseline up to approximately 5 years	Events were adjudicated by researchers as all-cause death. The number of all-cause deaths recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11.
Percentage of Participants With Cardiac Death	Baseline up to approximately 5 years	Description:Events were adjudicated by researchers as cardiac death. The number of all-cause deaths recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11.
Percentage of Participants With stroke	Baseline up to approximately 5 years	Description:Events were adjudicated by researchers as stroke. The number of all-stroke recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11
Percentage of Participants With transient ischemic attack	Baseline up to approximately 5 years	Description:Events were adjudicated by researchers as transient ischemic attack. The number of transient ischemic attack recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11
Percentage of Participants With acute coronary syndrome	Baseline up to approximately 5 years	Description:Events were adjudicated by researchers as acute coronary syndrome,. The number of acute coronary syndrome, recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11
Percentage of Participants With coronary angioplasty or revascularization	Baseline up to approximately 5 years	Description:Events were adjudicated by researchers as coronary angioplasty or revascularization. The number of coronary angioplasty or revascularization, recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11
Percentage of Participants With peripheral arterial angioplasty	Baseline up to approximately 5 years	Description:Events were adjudicated by researchers as peripheral arterial angioplasty. The number of peripheral arterial angioplasty recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11
Percentage of Participants With hospitalization for unstable angina or worsening heart failure	Baseline up to approximately 5 years	Events were adjudicated by researchers as endpoint hospitalization (hospitalization and stay in the emergency department due to heart failure, need for intravenous loop diuretics and/or doubling the dose of oral loop diuretics).; The number of hospitalization for unstable angina or worsening heart failure recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11
Percentage of Participants With Hospitalization	Baseline up to approximately 5 years	Events were adjudicated by researchers as endpoint hospitalization. The number of hospitalization for reasons other than the endpoint number 9, recorded from visit 0 (screening visit) to the last follow-up visit. Depending on the patient and the time of enrollment into the study, this corresponds to visit 7-11

Trial Locations

Locations (1)

Poznan University of Medical Sciences; 🇵🇱 Poznan, Wielkopolska, Poland