💬In plain words
What the trial is, and whether it could suit you
Primary biliary cholangitis (PBC) is a rare chronic, progressive, cholestatic liver disease that leads to cirrhosis and its life-threatening complications if undertreated. Ursodeoxycholic acid (UDCA) is the standard-of-care therapy for PBC. However, patients with an inadequate biochemical response to UDCA according to the Paris-2 criteria are still at high-risk of poor clinical outcome. In this situation of biochemical resistance to UDCA, bezafibrate 400 mg/d given in association with UDCA has been shown to improve the symptoms, biochemical response (BEZURSO study), histologic features, and possibly long-term clinical outcome. However, it has been shown that even patients with an adequate response to UDCA but persistent elevation in biochemical markers of cholestasis or liver inflammation, including alkaline phosphatases (ALP), gamma-glutamyl transpeptidase (GGT), transaminases, or total
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* Age ≥ 18 and \< 80 years
* Diagnosis of PBC based on at least 2 of the following criteria (EASL clinical practice guidelines 2017):
* Elevated ALP level
* Presence of antimitochondrial antibody (immunofluorescence titer ≥ 1:40 or positive antigen-specific test), specific antinuclear immunofluorescence (nuclear dots or perinuclear rims) or positive antigen-specific test for anti-gp210 or anti-Sp100 antibodies
* Records of histologic features suggestive of, or compatible with PBC
* UDCA therapy for the past 12 months (stable dose ≥ 12 mg/kg/d for ≥ 3 months prior to inclusion).
* Non-optimal response to UDCA defined by at least one of the following criteria (ratios of absolute values to ULN rounded to the first decimal digit) observed at least 2 times at ≥ 4 weeks interval in the past 3 months, including at the inclusion visit assessment:
* ALP \> 1.0 xULN
* GGT \> 3.0 xULN
* ALT or AST \> 1.0 xULN
* Total and conjugated bilirubin \> 1.0 xULN
* Women of childbearing potential must use at least one barrier contraceptive during the study and for at least 90 days after the last dose.
* Affiliation to a social security system (AME excepted).
* Signed informed consent.
Exclusion Criteria:
* Any of the following signs of advanced chronic liver disease:
* Total bilirubin \> 2.0 xULN
* Serum albumin \< 32 g/l
* Platelet count \< 100,000/mm3
* INR \> 1.3 or prothrombin index \< 60%
* Child-Pugh score B or C
* MELD score ≥ 14
* History ≤ 24 months or presence of cirrhotic decompensation
* Patients on the waiting list for LT
* GFR estimated by CKI-EPI equation \< 60 mL/min
* CPK \> 5.0 xULN
* AST or ALT \> 3.0 xULN
* History of LT
* Autoimmune hepatitis (AIH) overlap syndrome defined by at least 2 of the following 3 criteria including the histologic one:
* ALT \> 5.0 xULN
* IgG \> 20 g/l or presence of anti-smooth muscle or anti-SLA antibodies
* Histologic features characteristic of, or compatible with AIH
* Any other chronic hepatic comorbidities (HCV, HBV, NASH, alcoholic liver disease, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, celiac disease)
* Untreated hypo or hyperthyroidism (Hashimoto or Graves autoimmune thyroiditis)
* Conditions that may cause non-hepatic increases in ALP (Paget's disease, osteodystrophy, hyperparathyroidism, dysglobulinemia)
* Gilbert's syndrome or chronic hemolysis (hyperbilirubinemia with an unconjugated to total bilirubin ratio ≥ 75%)
* History of or established or suspected hepatocellular carcinoma
* History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted)
* Any severe comorbidity that may reduce life expectancy ≤ 2 years
* Pregnancy or lactating
* Known intolerance to bezafibrate
* Known hypersensitivity to bezafibrate, any of the components of Befizal© or other fibrates
* Known photosensitivity reactions or photoallergy reactions to fibrates
* Patient with congenital galactosemia, glucose malabsorption, or lactase deficiency because of presence of lactose in LP tablets of bezafibrate
* Participation in any other interventional study in the past 6 months
* Any of the following medications used in the past 3 months before inclusion: bezafibrate, fenofibrate, ciprofibrate, gemfibrozil, obeticholic acid, budesonide, any other systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, everolimus, methotrexate.
* Use of statins in the month before inclusion