What side effects are associated with this type of intervention?

Common treatments for heart failure include medications such as ACE inhibitors, beta-blockers, diuretics, and xanthine oxidase inhibitors like Allopurinol. ACE inhibitors can cause side effects such as cough, elevated blood potassium levels, and low blood pressure. Beta-blockers may lead to fatigue, cold hands and feet, and weight gain. Diuretics can result in electrolyte imbalances, dehydration, and kidney dysfunction. Allopurinol, a xanthine oxidase inhibitor, is generally well-tolerated but can cause skin rash, gastrointestinal upset, and in rare cases, severe hypersensitivity reactions.

What prior FDA approvals exist?

The FDA has approved several treatments for heart failure, including medications that target different pathways. While Allopurinol, a xanthine oxidase inhibitor, is being studied for its potential benefits in heart function, other approved treatments include ACE inhibitors (e.g., enalapril), angiotensin II receptor blockers (ARBs) like losartan, beta-blockers (e.g., metoprolol), and mineralocorticoid receptor antagonists (e.g., spironolactone). These medications help manage heart failure by reducing blood pressure, decreasing heart workload, and preventing fluid retention.

What other types of research exist?

Promising alternatives to Allopurinol for heart failure patients include Febuxostat, which is another xanthine oxidase inhibitor, and Losartan, an angiotensin II receptor blocker with uricosuric effects. These medications can help manage hyperuricemia and may offer cardiovascular benefits.

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Xanthine Oxidase Inhibitor

Allopurinol for Resistant Hypertension (RESIST Trial)

Q: What is the mechanism of action of this treatment?

Heart failure treatments often target the underlying mechanisms that contribute to the condition. Xanthine oxidase inhibitors like Allopurinol reduce oxidative stress and inflammation by inhibiting the enzyme xanthine oxidase, which is involved in the production of uric acid and reactive oxygen species. This can improve heart function and quality of life, particularly in patients with resistant hypertension. Other common treatments include ACE inhibitors and ARBs, which lower blood pressure and reduce the workload on the heart by inhibiting the renin-angiotensin-aldosterone system. Beta-blockers decrease heart rate and myocardial oxygen demand, while diuretics help reduce fluid overload. These treatments are crucial for managing symptoms, improving heart function, and reducing hospitalizations in heart failure patients.

Phase 2

Recruiting

Led By Louis J Dellitalia, MD

Research Sponsored by VA Office of Research and Development

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of resistant hypertension (defined as blood pressure greater than 140/90 mmHg at 2 clinic visits despite the use of 3 antihypertensive medications at pharmacologically effective doses)

Be older than 18 years old

Must not have

Already taking Allopurinol

Chronic kidney disease (estimated creatinine clearance < 60 ml/min)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 8 weeks

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Allopurinol may cause side effects like skin rash, digestive problems, liver issues and rarely more serious allergic reactions. Since it's often used to treat gout without major issues, severe side effects are uncommon but possible.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am currently taking Allopurinol.

Select...

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

Select...

I am on long-term steroid medication.

Select...

I have been diagnosed with heart artery disease.

Select...

I have a history of heart failure.

Select...

I have a condition that causes high blood pressure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 8 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~8 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 8 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

LV end-diastolic fractional shortening

LV end-diastolic mass index

LV end-diastolic mid-wall radius to wall thickness ratio

+6 more

Secondary study objectives

Brain Natriuretic Peptide

Diastolic Blood Pressure

Systolic Blood Pressure

+2 more

Side effects data

From 2019 Phase 3 trial • 530 Patients • NCT02017171

16%

Rash

12%

Upper respiratory tract infection

10%

Hypoglycaemia

Nasopharyngitis

Diabetic ketoacidosis

Urinary tract infection

Sinusitis

Influenza like illness

Pain in extremity

Bronchitis

Acute myocardial infarction

Abortion spontaneous

Osteomyelitis

Cardiac arrest

Chest pain

Amputation

Cellulitis

Pregnancy

Skin ulcer

Death

Asthma

Hyperemesis gravidarum

Road traffic accident

Myocardial infarction

Diarrhoea

Impaired gastric emptying

Pancreatitis acute

Angina unstable

Coronary artery disease

Cardiac failure congestive

Diabetic gastroparesis

Gastrointestinal haemorrhage

Pneumonia

Staphylococcal infection

Hyperglycaemia

Cerebrovascular accident

Renal failure acute

100%

80%

60%

40%

20%

Study treatment Arm

Allopurinol

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Allopurinol

1999

Completed Phase 4

~6150

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Heart failure treatments often target the underlying mechanisms that contribute to the condition. Xanthine oxidase inhibitors like Allopurinol reduce oxidative stress and inflammation by inhibiting the enzyme xanthine oxidase, which is involved in the production of uric acid and reactive oxygen species. This can improve heart function and quality of life, particularly in patients with resistant hypertension. Other common treatments include ACE inhibitors and ARBs, which lower blood pressure and reduce the workload on the heart by inhibiting the renin-angiotensin-aldosterone system. Beta-blockers decrease heart rate and myocardial oxygen demand, while diuretics help reduce fluid overload. These treatments are crucial for managing symptoms, improving heart function, and reducing hospitalizations in heart failure patients.