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

NCT05943821 | Recruiting Phase 3 DMC

• 1 other identifier: 2022/ABM/01/00027
• Study Type: interventional
• Target: 1,116
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Diseases; Uric Acid

Outcome Measures

Primary Outcomes (1)

• The occurrence of a major adverse cardiovascular event (MACE)

  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

  Baseline up to approximately 5 years

Secondary Outcomes (9)

• Percentage of Participants of all-cause death

  Baseline up to approximately 5 years

• Percentage of Participants With Cardiac Death

  Baseline up to approximately 5 years

• Percentage of Participants With stroke

  Baseline up to approximately 5 years

• Percentage of Participants With transient ischemic attack

  Baseline up to approximately 5 years

• Percentage of Participants With acute coronary syndrome

  Baseline up to approximately 5 years

Other Outcomes (12)

• Assessment of progression and/or development of organ complications and atherosclerosis, including: echocardiography

  Baseline up to the follow-up visit number 7 - approximately 3 years

• Assessment of progression and/or development of organ complications and atherosclerosis, including the assessment of incidence of atrial fibrillation

  Baseline up to the follow-up visit number 7 - approximately 3 years

• Assessment of progression and/or development of organ complications and atherosclerosis, including the assessment of end-stage kidney disease

  Baseline up to the follow-up visit number 7 - approximately 3 years

Study Arms (2)

Allopurinol

ACTIVE COMPARATOR

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).

Drug: Allopurinol 200 mg; Drug: Optional intervention

Placebo

PLACEBO COMPARATOR

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).

Drug: Allopurinol 200 mg; Drug: Optional intervention

Interventions

Allopurinol 200 mg DRUG

The intervention will occur after randomly allocating participants to the first group (G1), in which patients will receive allopurinol at an initial daily dose of 200 mg, or to the second group (G2), where they will receive a placebo. The placebo will be prepared as tablets with the same shape and appearance as the tested drug tablets, in the appropriate doses, and containing the same excipients. Participants will initially take one tablet of the medication daily in the morning. The physicians will dispense the drugs in packs of 30 tablets for the entire interval between visits (therapy 26 weeks ± 2 weeks). The patients will receive the medications during visit V1. The drugs will be prepared in identical packages, appropriately sealed, with a number for drug identification.

Also known as: Allopurinol

Allopurinol; Placebo

Optional intervention DRUG

Approximately 26 weeks(+/-2 weeks) after the start of the intervention, the efficacy of the treatment will be evaluated at the follow-up visit V2. Efficacy is defined as achieving a serum UA level below 5.0mg/dL for those with baseline levels \>5.0 to 7.0mg/dL or below 5.5mg/dL for those with baseline levels ≥7.0mg/dL. If insufficient therapy efficacy is noted, the initial allopurinol dose will be increased by 100mg (up to 300mg during V2). The dose may be increased by another 100mg at visit 3 and by another 100mg at the visit 4(up to 500mg during V4). In the placebo group, an appropriate preparation will be added so that the number of tablets corresponds to the group with the active substance. This treatment will be continued until the end of the bservation. Patients who meet their UA target concentration at visit V2 or V3, or V4, and those who fail to meet their target concentration at visit V4, will not have their dosing changed until the end of the follow-up.

Also known as: Please describe in more detail

Allopurinol; Placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: between 40-70 years old.
• Giving informed consent to participate in the study.
• Serum UA levels above 5 mg/dl within the last six months before the screening visit.
• Meeting at least one of the criteria defining high or very high CV risk includes:
• 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
• 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)
• 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.

You may not qualify if:

• Taking allopurinol, febuxostat or other hypouricemic drugs.
• Contraindications to taking allopurinol.
• Pregnant women, breastfeeding or planning pregnancy during the duration of the study.
• Hormonal therapy containing oestrogens.
• Active cancer process or disease in the last five years, excluding locally malignant tumours.
• Uncontrolled hypertension (mean value ≥ 180/110 mmHg seven days before screening visit) in home measurements despite using hypotensive drugs.
• \. Renal insufficiency with an eGFR \<45 ml/ min/1.73m2 (according to 2009 CKD-EPI recommendations: stage G3b, G4 and G5).
• Hypothyroidism or hyperthyroidism not in a state of euthyroidism.
• Confirmed coronary artery disease (defined as prior AMI, revascularization of the myocardium, confirmed presence of atherosclerotic plaques in coronary arteries on imaging studies).
• Heart failure in NYHA class III and IV.
• 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.

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead

Study Sites (1)

Poznan University of Medical Sciences

Poznan, Wielkopolska, 60-355, Poland

RECRUITING

Related Publications (1)

• Lewandowska K, Lipski D, Uruski P, Narkiewicz K, Januszewicz A, Wolf J, Prejbisz A, Rajzer M, Wiecek A, Tykarski A. Randomised, 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-19 syndrome: the ALL-VASCOR study protocol. BMJ Open. 2024 Jul 24;14(7):e075741. doi: 10.1136/bmjopen-2023-075741.

  PMID: 39053954 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Allopurinol

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Andrzej Tykarski, Prof MD

  Poznan University of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

Paweł Uruski, MD PhD

CONTACT

0048618546274; puruski@ump.edu.pl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 13, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: January 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)