Fenofibrate for Compensated Cirrhosis Patients With Primary Biliary Cholangitis

Официальное название

Fenofibrate Combined With Ursodeoxycholic Acid in Compensated Cirrhosis Patients With Primary Biliary Cholangitis Who Had an Inadequate Response to Ursodeoxycholic Acid

Обзор

The main objectives of the study were to assess the effects of fenofibrate on serum alkaline phosphatase, as a composite endpoint and on safety in participants with primary biliary cholangitis (PBC).

Подробное описание

This is a multi-center, randomized, placebo-controlled, parallel-group study that aims to assess the efficacy and safety of fenofibrate in patients with compensated cirrhosis PBC who had an inadequate biochemical response to UDCA. Fenofibrate or placebo 200 mg will be daily administered in combination with UDCA 13-15 mg/kg/d for 12 months.

Вмешательства

• Препарат Fenofibrate 200mg
  Fenofibrate 200mg/day
• Препарат Placebo
  1 tablet/ day
• Препарат UDCA
  UDCA 13-15mg/kg/day

Первичные конечные точки

• Percentage of patients with biochemical response [Срок оценки: 48 weeks]

Вторичные конечные точки (7)

• Percentage of patients having biochemical response [Срок оценки: 4, 12, 24 and 36weeks]
• Assessment of the pruritus and fatigue [Срок оценки: 4, 12, 24, 36, and 48 weeks]
• Percentage of patients having biological or clinical adverse events [Срок оценки: 4, 12, 24, 36, and 48 weeks]
• Percentage of patients having biological or clinical adverse events [Срок оценки: 4, 12, 24, 36, and 48 weeks]
• Percentage of patients having biological or clinical adverse events [Срок оценки: 4, 12, 24, 36, and 48 weeks]
• Percentage of patients having biological or clinical adverse events [Срок оценки: 4, 12, 24, 36, and 48 weeks]
• Survival without transplantation and hepatic impairment [Срок оценки: 48 weeks]

Критерии участия

Критерии включения

• Must have provided written informed consent
• Age 18-75 years;
• BMI 17-28 kg/m2
• Male or female with a diagnosis of PBC, by at least two of the following criteria:

• History of AP above ULN for at least six months;
• Positive AMA titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies;
• Documented liver biopsy result consistent with PBC.
• Diagnosis of compensated cirrhosis, as demonstrated by the presence of ≥ 1 of the following 4 diagnostic factor

• The histology was consistent with the diagnosis of liver cirrhosi;
• Endoscopy shows esophageal and gastric varices or ectopic varices of digestive tract, excluding non cirrhotic portal hypertension;
• Ultrasound or CT and other imaging examinations indicate the characteristics of liver cirrhosis or portal hypertension, such as splenomegaly, portal vein ≥ 1.3 cm, or liver stiffness measured by transient elastography>16.9 kPa;
• Abnormal laboratory inspection indicators (2 out of 4): 1) PLT < 100 × 109/L, and no other reason can be explained; 2) Serum albumin<35 g/L, excluding malnutrition or kidney disease and other causes; 3) INR > 1.3 or PT prolongation (stop thrombolytic or anticoagulant drugs for more than 7 days); 4) AST/PLT (APRI)>2）
• Incomplete response to UDCA defined by ALP > 1.67 x ULN
• Taking UDCA for at least 6 months (stable dose for ≥ 3 months) prior to Day 0

Критерии исключения

• History or presence of other concomitant liver diseases.
• ALT or AST > 5×ULN, TBIL > 3×ULN.
• If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
• Allergic to fenofibrate or ursodeoxycholic acid.
• Taking hepatotoxic drugs (e.g., dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than 2 weeks within 6 months, and long-term hormonal users.
• Recurrent variceal bleeding, poorly controlled hepatic encephalopathy or refractory ascites.
• Patients with a history of severe cardiac, cerebrovascular, renal, respiratory disease or functional failure, and psychiatric disorders (including those due to alcohol and drug abuse).
• Creatinine >1.5×ULN and creatinine clearance <60 ml/min.
• Currently using statins (such as pravastatin, fluvastatin, and simvastatin), other fibrates (such as gemfibrozil and bezafibrate), and drugs structurally similar to fenofibrate (like ketoprofen).
• Planned to receive an organ transplant or an organ transplant recipient.
• Needing Liver transplantation within 1 year according to the Mayo Rick score.
• Any other condition(s) that would compromise the safety of the subject or compromise

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 12 центров

• Peking Union Medical College Hospital — Пекин
• Sun Yat-sen Memorial Hospital — Гуанчжоу
• Henan Provincial People's Hospital — Чжэнчжоу
• Xiangya Hospital Central South University — Чанша
• Jiangsu Province Hospital — Нанкин
• The First Hospital of China Medical University — Шэньян
• Xijing Hospital — Сиань
• Yan'an University Affiliated Hospital — Yan’an
• … и ещё 4 центра

Идентификаторы

NCT: NCT05749822 · KY20222293-C-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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