Use of Bezafibrate in Patients With Primary Biliary Cirrhosis to Archive Complete Biochemical Response in Non-responders

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, treatment is based in the use of ursodeoxycholic acid (UDCA) at a daily dose of 13 to 15 mg/kg, without other treatment options. Patients with good or complete response to UDCA have more liver transplant-free survival and delay histologic progression compared to patients with partial or no response. Nowadays there is an estimated partial response to UDCA in approximately 30 to 50% of patients with PBC. There is a need for new second line management strategies for patients without a biochemical response to UDCA.

The addition of bezafibrate to the treatment of PBC patients with partial biochemical response to UDCA, will increase the biochemical response and improve the long term prognosis? And if so, which are the efficacy and security of bezafibrate in PBC patients without biochemical response?

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Treatments: Bezafibrate; Ursodeoxycholic Acid

Criteria

Inclusion Criteria:

• Primary biliary cirrhosis diagnosis made by 2 of the 3 criteria:

1. Biochemical evidence of cholestasis with an alkaline phosphatase rise of 1.5 times the upper normal limit.

2. Anti-mitochondrial antibodies positivity

3. Histopathologic evidence of a nonsuppurative cholangitis and small bile ducts destruction

• Use of ursodeoxycholic acid (UDCA) for at least 6 months at enrollment at a therapeutic dose (13 to 15 mg per Kg per day)

• Evidence of a suboptimal biochemical response to UDCA, defined by the presence of one of the Paris II criteria:

1. Alkaline phosphatase more or equal to 1.5 times the normal upper limit

2. Aspartate transaminase more or equal to 1.5 times the normal upper limit

3. Bilirubin more than 1 mg/dL

• Signed informed consent.

Exclusion Criteria:

• No informed consent given to enrollment

• Actual or history of hepatic decompensation (ascitis, variceal upper gastrointestinal bleeding, hepatic encephalopathy)

• Secondary immunosuppression caused by drugs (for example; steroids), use of statins or fibrates in the last 6 months. The investigators will exclude patients with medical indication of statin use.

• Coexistence of hepatopathy, chronic viral infections like C hepatitis virus, B virus and HIV. Excessive alcohol intake, autoimmune hepatitis, non-alcoholic fatty liver disease (diagnosed by histopathology), Wilson disease, hemochromatosis, celiac disease, choledocolithiasis, non-controlled thyroid disease

• Post liver transplant

• Known allergy or intolerance to fibrates

• Pregnancy or women who desire to become pregnant

• Chronic kidney disease with a glomerular filtration less than 60 ml/min

• Patients under total anticoagulation with vitamin K antagonist