Allopurinol in Patients With Refractory Angina to Improve Ischemic Symptoms

NCT04368819 | Unknown Phase 2

• 2 other identifiers: SDC 4781/18/1322018/22588-3
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Despite numerous advances in medical treatment and revascularization procedures for the treatment of patients with stable angina, debilitating symptoms that are unresponsive to conventional therapy may occur in patients unsuitable for revascularization, a condition known as refractory angina. Allopurinol, a methylxanthine oxidase inhibitor, is widely used in the treatment of gout and asymptomatic hyperuricemia. On the other hand, the anti-ischemic effects of allopurinol have been the subject of increasing interest. Therefore, the investigators will study the safety and efficacy of allopurinol in alleviating ischemic symptoms in patients with refractory angina already on optimal medical therapy.

Conditions

Refractory Angina

Keywords

angina; coronary artery disease; myocardial ischemia; treatment; allopurinol; cardiopulmonary exercising test; oxidative stress; stress echocardiogram

Outcome Measures

Primary Outcomes (1)

• Increase in total exercise time (seconds) assessed by CPET

  Total exercise duration during a maximal, symptom-limited cardiopulmonary exercise testing

  16 weeks

Secondary Outcomes (5)

• Number of angina attacks per week

  16 weeks

• Short-acting nitrates intake per week

  16 weeks

• Relative decrease in stress-induced myocardial ischemia during exercise echocardiogram

  16 weeks

• Relative change in the levels of oxidative stress biomarkers

  16 weeks

• Relative change in endothelium-dependent vasodilation during reactive hyperemia in the forearm

  16 weeks

Other Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  16 weeks

Study Arms (2)

Allopurinol

ACTIVE COMPARATOR

Allopurinol 300mg P.O. once daily for four weeks followed by allopurinol 300mg P.O. twice daily for 12 weeks.

Drug: Allopurinol 300 MG

Placebo

PLACEBO COMPARATOR

Placebo pills indistinguishable from the active comparator given P.O. once daily for four weeks, followed by twice daily for 12 weeks.

Drug: Placebo oral tablet

Interventions

Allopurinol 300 MG DRUG

Allopurinol 300mg once daily for four weeks followed by allopurinol 300mg twice daily for 12 weeks

Also known as: Zyloric

Allopurinol

Placebo oral tablet DRUG

Placebo 300mg once daily for four weeks followed by allopurinol 300mg twice daily for 12 weeks

Also known as: Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of stable angina in functional class (CCS) ≥ 2 for at least three months in patients taking maximally tolerated doses of at least three classes of antianginal agents
• Documentation of myocardial ischemia by any provocative functional test (exercise test, stress echocardiogram, myocardial perfusion scintigraphy or cardiac resonance)
• Signature of the Informed Consent Form

You may not qualify if:

• Left ventricular dysfunction defined by LVEF \< 30% on transthoracic echocardiogram
• Significant concomitant valve disease
• Chronic renal failure stage 4 or 5 (GFR \< 30mL/min/1.73m2 calculated by the MDRD equation
• Significant liver dysfunction (Child-Pugh class C) or MELD value ≥ 15 calculated from creatinine, total bilirubin, and INR values
• Current use of warfarin
• Prior use of allopurinol within three months of randomization
• Pregnant and lactating women

Sponsors & Collaborators

• Ministry of Health, Brazil: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator
• InCor Heart Institute: collaborator

Study Sites (1)

Heart Institute

São Paulo, São Paulo, 05403-000, Brazil

RECRUITING

Related Publications (1)

• Noman A, Ang DS, Ogston S, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet. 2010 Jun 19;375(9732):2161-7. doi: 10.1016/S0140-6736(10)60391-1. Epub 2010 Jun 9.

  PMID: 20542554 BACKGROUND

MeSH Terms

Conditions

Angina Pectoris; Coronary Artery Disease; Myocardial Ischemia

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Luis Henrique W Gowdak, MD, PhD

  Heart Institute (InCor-HCFMUSP)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luis Henrique W Gowdak, MD, PhD

CONTACT

+55-11-26615000; luis.gowdak@incor.usp.br

Renato P Azevedo, MD

CONTACT

+55-11-32877441; renatoslz@yahoo.com.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The placebo pills will be manufactured to be indistinguishable from the active treatment and dispensed by a registered pharmacist (who also will be blind to the intervention assigned to each individual participant) from our center.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Scientist

Model Details: Patients will randomly be assigned to receive either placebo or allopurinol 300mg once daily for four weeks, up titrate to 600mg for another 12 weeks for a total of 16 weeks of treatment.

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 30, 2020
• Study Start: March 3, 2021
• Primary Completion: September 30, 2021
• Study Completion: December 31, 2021
• Last Updated: February 24, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)