Clinical trial NCT05474560: Febuxostat Versus Allopurinol on Hepatic Steatosis in MAFLD Patients
Official title: Allopurinol Versus Febuxostat: A New Approach for Management of Hepatic Steatosis in Metabolic-Associated Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non-Alcoholic Fatty Liver Disease
Hyperuricemia
Keywords: Fatty liver disease
Hyperuricemia
Allopurinol
Febuxostat
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2022-07-26
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A total of 90 subjects are enrolled in this study. After the initial screening, the subjects were randomly divided into the control group and the drug treatment group. The control group was given lifestyle intervention for 24 weeks, and the experimental group was given febuxostat oral therapy or allopurinol oral therapy on the basis of lifestyle intervention.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in hepatic steatosis .
timeFrame: 3 months
Secondary outcomes:
measure: Serum uric acid.
timeFrame: three months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: National Hepatology and tropical medicine research institute
Study officials:
affiliation: Ain Shams University
name: Sarah Ma Zaki, Ass.Prof.
role: STUDY_DIRECTOR
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