Allopurinol for Resistant Hypertension (RESIST Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: VA Office of Research and Development
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.
12345How 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.
26789Eligibility 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
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.
I have been diagnosed with heart artery disease.
I have a history of heart failure.
I have a condition that causes high blood pressure.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Allopurinol - African American VeteransExperimental Treatment1 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 United States, European Union, Canada, Japan, Australia for the following indications:
🇺🇸 Approved in United States as Zyloprim for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
🇪🇺 Approved in European Union as Zyloric for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
🇨🇦 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
🇦🇺 Approved in Australia as Allopurinol for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Birmingham VA Medical Center, Birmingham, ALBirmingham, AL
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Who is running the clinical trial?
VA Office of Research and DevelopmentLead Sponsor
References
[Side effects off allopurinol]. [2013]Allopurinol is generally considered to be a safe and well tolerated drug. We report one patient with a serious effect from allopurinol, a serious exfoliative rash and signs of allopurinol hypersensitivity syndrome. Only after considerable diagnostic delay and patient morbidity, signs and symptoms were associated with the drug. The patient recovered when the medication was withdrawn. Data from the Norwegian reporting system for side effects of drugs for the period 1973-2003 show a wide range of side effects of allopurinol and even some fatalities. The indication for treatment must be carefully considered. Impaired renal function, ampicillin and thiazide diuretics increase the risk of serious hypersensitivity reactions.
Allopurinol desensitization with A 2 weeks modified protocol in an elderly patients with multiple comorbidities: a case report. [2020]Allopurinol is an effective urate-lowering drug that is well tolerated by the majority of patients. Patients with chronic renal insufficiency have an increased risk of hypersensitivity reactions with allopurinol.
Milurit's place in therapy. [2013]After a brief review of the history of allopurinol therapy the mechanism of action, interactions with other drugs, side-effects, indications and contra-indications of Milurit (100 mg allopurinol per tab, EGIS Pharmaceuticals, Budapest) in adults and children, and the dosage of the drug have been discussed. It has been emphasized that allopurinol is an effective but not the sole means in the treatment of clinical processes accompanied by hyperuricaemia. The adequate choice of a drug in a given indication field not only improves the therapeutic results but prevents the development of one part of the side-effects such as among others the severe allopurinol hypersensitivity syndrome which often has a lethal outcome.
Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions. [2018]Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate
Cardiovascular Safety Evaluation of Febuxostat and Allopurinol: Findings from the FDA Adverse Event Reporting System. [2023]Febuxostat and allopurinol are the most commonly used uric acid-lowering medications, and their safety is of great concern, especially the cardiovascular adverse reactions associated with febuxostat. We propose to study the cardiovascular toxicity of febuxostat and allopurinol using the FDA Adverse Event Reporting System (FAERS) database.
The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout. [2022]The objectives of this study were to establish if, and to what extent, benzbromarone affects allopurinol/oxypurinol kinetics, and to compare the uric acid lowering capabilities of Allomaron (allopurinol 100 mg plus benzbromarone 20 mg) with the effects of allopurinol alone in patients with confirmed gout. We studied 14 adult men in an open randomized cross-over study. After a 14 day run-in period with Zyloprim (2 x 100 mg allopurinol tablets in the morning), the patients were randomly allocated to morning doses of either Allomaron (2 tablets) or Zyloprim (2 tablets). Seven days later cross-over was effected and the alternative treatment was taken for a further 7 days. On days 7 and 14 the patients came into hospital and venous blood samples were taken over 24 h for allopurinol and oxypurinol assays by HPLC. Serum uric acid was determined on days -14, 1, 7, and 14. Benzbromarone lowered plasma oxypurinol concentrations (Allomaron/Zyloprim mean ratio of AUC0-->24 was 59%; 95% confidence interval 54-64%), but did not affect plasma allopurinol concentrations. Despite this pharmacokinetic interaction of benzbromarone with allopurinol, resulting in lower plasma concentrations of oxypurinol, Allomaron was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone.
HLA-DR9 and DR14 are associated with the allopurinol-induced hypersensitivity in hematologic malignancy. [2022]Allopurinol, a widely used urate-lowering agent, is a leading cause of severe cutaneous adverse reactions (SCARs), especially in patients with HLA-B*58:01. Despite its routine use for the prevention of tumor lysis-related hyperuricemia prior to chemotherapy, the risk of allopurinol-induced hypersensitivity has not been investigated in patients with hematologic malignancies. This retrospective cohort study was conducted to investigate the incidence and risk factors of allopurinol-induced hypersensitivity in patients at least 18 years of age with hematologic malignancies. We reviewed 463 patients who had ever taken allopurinol for the prevention of hyperuricemia prior to chemotherapy and had undergone serologic HLA typing as a pre-transplant evaluation from January 2000 to May 2010. Thirteen (2.8%) patients experienced maculopapular eruptions (MPE) and none experienced SCARs. Among subtypes of underlying hematologic malignancies, percentage of chronic myeloid leukemia was significantly higher in the allopurinol hypersensitivity group compared with the tolerant group (23.1% (3/13) vs. 5.9% (26/440), P = 0.044). According to HLA subtypes, the incidence of allopurinol-induced MPE was 4.0% in HLA-B58 (+) patients (2/50) and 2.7% in HLA-B58 (-) patients (11/403) but this difference was statistically insignificant. In contrast to HLA-B58, the frequencies of DR9 and DR14 were significantly higher in the allopurinol-induced MPE group compared with the allopurinol tolerant group (38.5% (5/13) vs. 13.6% (53/443), P = 0.019, and 38.5% (5/13) vs. 15.6% (41/440), P = 0.038, respectively). In conclusion, HLA-DR9 and DR14, but not HLA-B58, are associated with hypersensitivity reaction by allopurinol when administered in patients with hematologic malignancy prior to chemotherapy.
Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient. [2022]A major obstacle to the treatment of hyperuricemia in patients allergic to allopurinol is the limited availability of suitable, equally effective, alternative, urate-lowering drugs. Conventional uricosuric drugs, including probenecid and sulfinpyrazone, are recommended for allopurinol- intolerant patients with gout and "underexcretion" hyperuricemia who have normal renal function and no history of nephrolithiasis. Therapeutic options in those in whom traditional uricosuric drugs are contraindicated, ineffective, or poorly tolerated include slow oral desensitization to allopurinol and cautious administration of oxipurinol. Allopurinol desensitization is useful particularly in those who have failed other treatment modalities. If available (as in Europe, South Africa, and Japan), benzbromarone may be tried in patients with gout and mild-to-moderate renal insufficiency. Recombinant urate oxidase can be used in the short-term prophylaxis and treatment of chemotherapy- associated hyperuricemia in patients with lymphoproliferative and myeloproliferative disorders. Hyperuricemia and gout occur with increased frequency in cyclosporine-treated allograft transplant recipients. The management of gout in these patients is complicated by two main factors: cyclosporine-induced renal impairment, and interactions with medications used to preserve the allograft.
Allopurinol adherence and its predictors in gout: a national cohort study in US veterans. [2022]Allopurinol is a frequently used, effective, and affordable medication for gout. However, poor adherence to allopurinol is a key reason for patients not reaching treatment goals. The aim of this study was to comprehensively assess factors associated with high allopurinol adherence in gout.