Allopurinol as a preventive drug in patients with high and very high cardiovascular risk, taking into account the presence of the long-COVID syndrome.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uniwersytet Medyczny Im. Karola Marcinkowskiego W Poznaniu

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

28 Mar 2024 → ongoing

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-517610-15-00

EudraCT number

2022-003573-32

ClinicalTrials.gov

NCT05943821

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

In patients with very high and high cardiovascular risk, the use of allopurinol will reduce cardiovascular risk, in the entire study population and in the group over 60 years of age.

Conditions and MedDRA coding

hyperuricemia, hypertension, ischemic stroke, intracerebral haemorrhage, TIA, heart failure, peripheral arterial disease, atrial fibrillation, diabetes mellitus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age: between 40 and 70 years old
2. Giving informed consent to participate in the study
3. Serum uric acid above 5mg/dl within the last 6 months for screening
4. At least one of the criteria for very high or high cardiovascular risk: a. calculated 10-year risk of death from cardiovascular causes according to SCORE2 >2.5% for patients <50 years of age or ≥5% for patients ≥50 years of age b. documented occurrence of cardiovascular diseases (cerebrovascular disease: ischemic stroke, intracerebral bleeding, TIA; heart failure regardless of the etiology NYHA I - II, peripheral arterial disease PAD, atrial fibrillation (de novo or ever in history) c. diabetes or hypertension complicated by organ damage: i. increase in vascular stiffness: pulse pressure ≥ 60 mmHg, and/or cervicofemoral pulse wave velocity > 10 m/s ii. features of left ventricular hypertrophy on echocardiography or electrocardiography iii. elevated albumin-creatinine ratio in the urine sample (30-300 mg/g) iv. ankle-brachial index < 0.9.

Exclusion criteria 15

1. Taking allopurinol, febuxostat or other hypouricemic drugs within the last 6 months for screening.
2. Heart failure in class III and IV according to NYHA
3. Taking preparations: azathioprine, mercaptopurine, cyclosporine.
4. Participation in another clinical trial on a medicinal product or medical device within the last 3 months or 5 half-lives, whichever is longer
5. Diagnosed liver cirrhosis regardless of etiology.
6. Aspartate and/or alanine transaminase activity exceeding 3 times the upper limit of normal during the screening period
7. Contraindications to taking allopurinol preparation
8. Women who are pregnant, lactating or planning to become pregnant during the study.
9. Hormone therapy containing estrogens.
10. Active neoplastic process or neoplastic disease in the last 5 years, excluding locally malignant neoplasms.
11. Uncontrolled hypertension (mean value ≥ 180/110 mmHg on the 7th day preceding the screening visit) in home measurements despite the use of antihypertensive drugs.
12. Renal failure with renal filtration rate eGFR <30 ml/min/ 1.73 m2 (according to recommendations of 2009 CKD-EPI G3b, G4 and G5).
13. Hypothyroidism or hyperthyroidism not in a euthyroid state.
14. Confirmed ischemic heart disease (defined as: history of AMI, myocardial revascularization or or the occurrence of angina symptoms accompanied by atherosclerotic changes in coronary vessels > 50% detected in computed tomography or coronary angiography).
15. Any condition or circumstance that, in the investigator’s judgment, could interfere with conduct of the study per protocol or with obtaining written informed consent, e.g., alcohol, drug, or other substance abuse or dependence.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of a major cardiovascular event (MACE) such as all cause death, cardiac death, stroke/TIA, acute coronary syndrome, coronary artery angioplasty or revascularization, peripheral arterial angioplasty, hospitalization for unstable angina, or worsening heart failure (hospitalization and stay in the emergency room / Hospital Emergency Department due to heart failure, the need for intravenous loop diuretic and/or doubling the dose of oral loop diuretic).

Secondary endpoints 8

1. Individual MACE components alone or in combination
2. Hospitalisation for reasons other than the primary endpoint.
3. The assessment of the progression and/or development of organ complications and the development and/or progression of atherosclerosis including: echocardiography; the assessment of the incidence of atrial fibrillation in an electrocardiographic examination ; assessment of abdominal aorta diameter in uultrasound examination; the assessment of the intima-media complex and atherosclerotic plaques in the Doppler ultrasound of the carotid arteries; the assessment of the ankle-brachial index;
4. The occurrence of long-COVID-19 symptoms.
5. The assessment of treatment efficacy: the attainment of target serum uric acid levels of 5 mg/dL or 5.5 mg/dL depending on baseline values.
6. The assessment of other laboratory parameters: estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio, urinary albuminuria; HbA1c; lipid profile; plasma C reactive protein concentrations; activity of aspartate and alanine transaminases (AspAT, AlAT).
7. The assessment of the frequency of side effects.
8. The assessment of changes in participants’ CVs based on the Systematic Coronary Risk Evaluation (SCORE) 2 scale

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uniwersytet Medyczny Im. Karola Marcinkowskiego W Poznaniu

Sponsor organisation

Uniwersytet Medyczny Im. Karola Marcinkowskiego W Poznaniu

Address

Ul. Aleksandra Fredry 10

City

Poznan

Postcode

61-701

Country

Poland

Scientific contact point

Organisation

Uniwersytet Medyczny Im. Karola Marcinkowskiego W Poznaniu

Contact name

Sponsor Representative

Public contact point

Organisation

Uniwersytet Medyczny Im. Karola Marcinkowskiego W Poznaniu

Contact name

Sponsor Representative

Third parties 2

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications