Clinical trial NCT05943821: The Effect of Allopurinol on the Risk of Cardiovascular Events in Patients with Cardiovascular Risk
Official title: A Randomized, Double-blind, Placebo-controlled Study Evaluating the Effect of Allopurinol on the Risk of Cardiovascular Events in Patients with High and Very High Cardiovascular Risk, Including the Presence of Long-COVID Syndrome.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cardiovascular Diseases
Uric Acid
Lead sponsor: Poznan University of Medical Sciences
Sponsor class: OTHER
First posted: 2023-07-13
Enrollment: 1116
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The occurrence of a major adverse cardiovascular event (MACE)
timeFrame: Baseline up to approximately 5 years
Secondary outcomes:
measure: Percentage of Participants of all-cause death
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With Cardiac Death
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With stroke
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With transient ischemic attack
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With acute coronary syndrome
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With coronary angioplasty or revascularization
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With peripheral arterial angioplasty
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With hospitalization for unstable angina or worsening heart failure
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With Hospitalization
timeFrame: Baseline up to approximately 5 years
Other outcomes:
measure: Assessment of progression and/or development of organ complications and atherosclerosis, including: echocardiography
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Assessment of progression and/or development of organ complications and atherosclerosis, including the assessment of incidence of atrial fibrillation
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Assessment of progression and/or development of organ complications and atherosclerosis, including the assessment of end-stage kidney disease
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Assessment of progression and/or development of organ complications and atherosclerosis, including Ultrasound examination
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Assessment of progression and/or development of organ complications and atherosclerosis, including Doppler ultrasound of carotid arteries
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Assessment of progression and/or development of organ complications and atherosclerosis, including the assessment of ankle-brachial index
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Assessment of progression and/or development of organ complications and atherosclerosis, including the assessment of pulse wave velocity
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Occurrence of long-COVID symptoms
timeFrame: Baseline up to approximately 5 years
measure: The assessment of treatment efficacy
timeFrame: Baseline up to the follow-up visit number 7- approximately 3 years
measure: Assessment of the laboratory parameters
timeFrame: Baseline up to the follow-up visit number 7 - approximately 3 years
measure: Assessment of frequency of side effects
timeFrame: From the first dose of allopurinol or placebo until the end of the observation period (approximately 3-5 years)
measure: Assessment of changes in participants' cardiovascular risk
timeFrame: Baseline up to approximately 5 years
Locations:
city: Poznan
country: Poland
facility: Poznan University of Medical Sciences
state: Wielkopolska
Study officials:
affiliation: Poznan University of Medical Sciences
name: Andrzej Tykarski, Prof MD
role: STUDY_DIRECTOR
References: