Febuxostat Versus Allopurinol on Hepatic Steatosis in MAFLD Patients

Phase 4

Completed

• Conditions: Non-Alcoholic Fatty Liver Disease; Hyperuricemia
• Interventions: Behavioral: Life style intervention; Drug: Allopurinol (100 mg/day) plus lifestyle intervention; Drug: Febuxostat 40 mg plus lifestyle intervention

• Registration Number: NCT05474560
• Lead Sponsor: Ain Shams University

Brief Summary

Metabolic associated fatty liver disease (MAFLD) is the most common and harmful chronic liver disease, and it is increasingly diagnosed in many developed and developing countries.

Previous studies suggested a significant association between hyperuricemia and MAFLD and that hyperuricemia plays a causal role in the development of MAFLD.

Xanthine oxidase is a key enzyme in uric acid metabolism, and It thus can be considered as is a therapeutic target for MAFLD, so long-term urate-lowering therapy may play a role in amelioration of MAFLD by controlling uric acid levels. So, this study is conducted to assess the effect of controlling hyperuricemia using different xanthine oxidase inhibitors on amelioration of MAFLD.

Detailed Description

The aim of this study is to evaluate the effect of urate lowering therapy on improvement of steatosis in metabolic associated fatty liver disease (MAFLD) patients with hyperuricemia, by comparing two xanthine oxidase inhibitors allopurinol (100 mg/day), versus Febuxostat (40 mg/day), versus lifestyle intervention.

Primary Outcome: Regression of hepatic steatosis. Secondary Outcome: Improvement of Serum uric acid and incidence of hepatotoxicity.

Study design: This study is a prospective, interventional three arm study. Setting: Patients will be recruited from the National Hepatology and Tropical Medicine Research institute, Cairo, Egypt.

Study Timeline

• Study Start: 2022-01-01
• Study First Submitted: 2022-07-13
• Study First Submitted QC: 2022-07-23
• Study First Posted: 2022-07-26
• Primary Completion: 2023-01-28
• Study Completion: 2023-01-28
• Status Verified: 2023-02
• Last Update Submitted: 2023-07-30
• Last Update Posted: 2023-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Ages 18-65.

• Males and Females

• Metabolic syndrome according to the NCEP ATP III definition [13]: present of three or more of the following five criteria are met:

  • Waist circumference over 40 inches (men) or 35 inches (women), Central obesity - defined as waist circumference ≥ 102 cm for Men and ≥ 88 cm for women
  • Blood pressure over 130/85 mmHg,
  • Basting triglyceride (TG) level over 150 mg/dl,
  • Fasting high-density lipoprotein (HDL) cholesterol level less than 40 mg/dl (men) or 50 mg/dl (women),
  • Fasting blood sugar over 100 mg/dl.

• Serum uric acid levels of > 420μmol/L (>7 mg/dL) in men and >360 μmol/L (>6 mg/dL) women.

Exclusion Criteria

• Renal insufficiency defined by serum creatinine > 2.0 mg/dl.

  • Patients with obvious abnormal liver function: serum transaminase (ALT, AST, one of them) exceed 2 times the upper limit of normal reference value.
  • Have a history of viral hepatitis, or serological examination suggests hepatitis virus infection, or have a history of other liver diseases.
  • Complementation with diabetes, or fasting blood glucose >7.8mmol/L, or HbA1c >7.5%.
  • Severe hypertension, blood pressure ≥ 160/100 mmHg.
  • A history of allergy to febuxostat and allopurinol; in the acute active phase of gout.
  • Drinking equivalent to alcohol intake ≥30g/d(male), ≥20g/d(female).
  • Complicated coronary heart disease.
  • Cardiac dysfunction (cardiac function grade 2 or above).
  • Patients with asthma and other respiratory diseases.
  • Intestinal diseases such as inflammatory bowel disease.
  • Any history of systemic malignancy in the past 5 years.
  • Use of uric-lowering drugs in the 4 weeks before screening: febuxostat, allopurinol, benzbromarone.
  • Morbid obesity (BMI>37.5kg/m2).
  • Triglyceride ≥5.0 mmol/L was found to be significantly abnormal in baseline examination.
  • had received systemic hormone or immunosuppressive therapy within 3 months prior to screening or expected to receive hormone or immunosuppressive therapy in the future.
  • Use of other drugs affecting uric acid metabolism were adjusted within 4 weeks before screening: losartan, fenofibrate, irbesartan, thiazide diuretics, loop medullar diuretics, compound antihypertensive agents containing diuretics.

Other drugs that may affect liver fat content were taken within 4 weeks before screening.

• Women who are lactating or pregnant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
lifestyle intervention	Life style intervention	diet and exercise
Allopurinol group	Allopurinol (100 mg/day) plus lifestyle intervention	Allopurinol (100 mg/day) plus lifestyle intervention
Febuxostat group	Febuxostat 40 mg plus lifestyle intervention	Febuxostat (40 mg/day) plus lifestyle intervention

Primary Outcome Measures

Name	Time	Method
Change in hepatic steatosis .	3 months	FibroScan instrument measures fibrosis (scarring) and steatosis (fatty changes) in your liver. Fatty changes are when fat builds up in your liver cells.; FibroScan steatosis result (CAP score): decibels per meter(dB/M). it ranges from 100 to 400 dB/m. The fibrosis result is measured in kilopascals (kpa). It is normaly between 2 and 6 kpa.

Secondary Outcome Measures

Name	Time	Method
Serum uric acid.	three months	change in serum uric milligrams/deciliter (mg/dl) in hyperuricemia patients. Normal values are 1.5 to 6.0 (mg/dl).

Trial Locations

Locations (1)

National Hepatology and tropical medicine research institute; 🇪🇬 Cairo, Egypt