Allopurinol for Resistant Hypertension

(RESIST Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Louis J Dellitalia, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: VA Office of Research and Development

Must be taking: Antihypertensives

Must not be taking: Allopurinol, Steroids

Disqualifiers: Heart failure, Chronic kidney disease, others

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if Allopurinol, a gout medication, can improve heart function and quality of life in African American Veterans with high blood pressure that doesn't respond well to typical treatments. The medication works by blocking an enzyme that contributes to heart problems. Allopurinol has been used to lower blood pressure and has protective effects on blood vessels, though its benefits in older individuals remain unclear.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves participants with resistant hypertension already on three antihypertensive medications, it seems likely you will continue your current treatment.

Is allopurinol generally safe for humans?

Allopurinol is generally considered safe and well-tolerated, but it can cause serious skin reactions, especially in people with certain genetic markers (HLA-B*58:01) or kidney problems. It's important to monitor for side effects and consult a doctor if any occur. ^{1 2 3 4 5}

How is the drug Allopurinol unique in treating resistant hypertension?

Allopurinol is unique because it is primarily a urate-lowering drug used for conditions like gout and hyperuricemia, but its use in resistant hypertension is novel. It works by reducing uric acid levels, which may have a role in lowering blood pressure, offering a different mechanism compared to traditional blood pressure medications. ^{2 6 7 8 9}

Research Team

Louis J Dellitalia, MD

Principal Investigator

Birmingham VA Medical Center, Birmingham, AL

Eligibility Criteria

This trial is for African American veterans in Birmingham, AL with resistant hypertension, which means their blood pressure remains high despite taking three different blood pressure medications. They must not have heart failure, kidney disease, coronary artery disease or be on chronic steroid therapy. Also excluded are those already on Allopurinol or with conditions that prevent safe CMR imaging.

Inclusion Criteria

Criterion: You are of African American descent.

This criterion is very broad and needs more context. "Veteran" could refer to someone who has served in the military, but it's not clear how this relates to a clinical trial exclusion criteria. Can you provide more information or context for this criterion?

My blood pressure remains high despite taking 3 different blood pressure medications.

Exclusion Criteria

I am currently taking Allopurinol.

My kidneys do not work well (poor kidney function).

I am on long-term steroid medication.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Allopurinol (300mg/daily) for 4 weeks, then 600mg/daily for an additional 4 weeks if tolerated

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Allopurinol (Xanthine Oxidase Inhibitor)

Trial Overview The study tests whether Allopurinol can improve heart function and quality of life over an 8-week period in African Americans who have high blood pressure that doesn't respond to standard treatments. It explores if lowering xanthine oxidase levels with this medication used for gout makes a difference.

Participant Groups

Group I: Allopurinol - African American Veterans Experimental Treatment 1 Intervention

Subjects will receive Allopurinol (300mg/daily) for 4 weeks. If tolerated, dose will be increased to 600mg/daily for an additional 4 weeks. Subjects will take Allopurinol (300-600mg/daily) for 8 weeks total

Allopurinol is already approved in Canada, Japan for the following indications:

Approved in Canada as Allopurinol for:

• Gout
• Kidney stones
• High uric acid levels after chemotherapy

Approved in Japan as Allopurinol for:

• Gout
• Kidney stones
• High uric acid levels after chemotherapy

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Findings from Research

Allopurinol is generally safe, but there is a risk of serious side effects, including a potentially life-threatening hypersensitivity syndrome, as demonstrated in a case where a patient developed a severe exfoliative rash after taking the drug.

Data from Norway (1973-2003) indicate that allopurinol can cause a variety of side effects, including fatalities, especially in patients with impaired renal function or those taking certain medications like ampicillin and thiazide diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Side effects off allopurinol]. Rødevand, E., Sletvold, O., Kvande, KT.[2013]

A 75-year-old male with gout and renal insufficiency successfully underwent a modified 2-week desensitization protocol for allopurinol, which is typically associated with hypersensitivity reactions in patients with renal issues.

The desensitization allowed the patient to safely tolerate a full dose of 300 mg/day of allopurinol, leading to normalization of his urate levels without any adverse reactions, demonstrating a safe approach for managing gout in patients with multiple comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allopurinol desensitization with A 2 weeks modified protocol in an elderly patients with multiple comorbidities: a case report. Dursun, AB., Sahin, OZ.[2020]

Allopurinol is an effective treatment for conditions associated with high uric acid levels, but it should not be the only option considered, as careful selection of therapy can enhance outcomes and minimize side effects.

The use of allopurinol carries risks, including the potentially life-threatening allopurinol hypersensitivity syndrome, highlighting the importance of appropriate dosing and monitoring in both adults and children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Milurit's place in therapy. Gömör, B., Szebenyi, B.[2013]

Febuxostat is associated with a higher risk of cardiovascular adverse events, including heart failure and ischemic heart disease, particularly in elderly gout patients, compared to allopurinol.

The analysis of 64 quarters of data from the FDA Adverse Event Reporting System revealed that febuxostat had 2,939 reports of cardiovascular adverse events, while allopurinol had 25,219, indicating a significant concern for febuxostat's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety Evaluation of Febuxostat and Allopurinol: Findings from the FDA Adverse Event Reporting System. Bai, Y., Wu, B., Gou, L., et al.[2023]

Benzbromarone significantly lowers plasma concentrations of oxypurinol when combined with allopurinol, but does not affect allopurinol levels, indicating a pharmacokinetic interaction.

The combination of allopurinol and benzbromarone (Allomaron) is more effective in lowering serum uric acid levels in gout patients compared to allopurinol alone, likely due to benzbromarone's uricosuric effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout. Müller, FO., Schall, R., Groenewoud, G., et al.[2022]

For patients allergic to allopurinol, alternative treatments for hyperuricemia include uricosuric drugs like probenecid and sulfinpyrazone, but these are only suitable for those with normal kidney function and no history of kidney stones.

In cases where traditional treatments are ineffective or not tolerated, options like slow oral desensitization to allopurinol or the use of oxipurinol can be beneficial, especially for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient. Fam, AG.[2022]

References

1. Norway pubmed.ncbi.nlm.nih.gov

[Side effects off allopurinol]. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Allopurinol desensitization with A 2 weeks modified protocol in an elderly patients with multiple comorbidities: a case report. [2020]

3. Hungary pubmed.ncbi.nlm.nih.gov

Milurit's place in therapy. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety Evaluation of Febuxostat and Allopurinol: Findings from the FDA Adverse Event Reporting System. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

HLA-DR9 and DR14 are associated with the allopurinol-induced hypersensitivity in hematologic malignancy. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Allopurinol adherence and its predictors in gout: a national cohort study in US veterans. [2022]