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

NCT ID: NCT02937012

Last Updated: 2018-04-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-31

Study Completion Date

2019-12-31

Brief Summary

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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?

Detailed Description

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There are case reports and pilot studies in patients with primary biliary cholangitis (PBC) In the literature in which the effect of fibrates (specially bezafibrate) on the improvement of biochemical cholestasis have been seen, however the clinical benefit (survival, mortality, fatigue, pruritus) has not been reported and likewise the response criteria used in previous studies is very heterogeneous. In previous studies, bezafibrate has been proved to be a secure drug in this patients, with few adverse events, also it is an economic and of easy access drug. For all this the investigators intent to study the utility of bezafibrate as an additional treatment in PBC patients without response to UDCA.

This is a randomized, placebo-controlled, parallel-group study designed to enroll a total of 34 patients with diagnosis of PBC without a complete response to the use of UDCA for more than a year, then the participants will be divided by randomization to receive bezafibrate or placebo, resulting in a total of two groups of 17 patients each. Both groups will be followed every 3 months for a total of 1 year with clinical and laboratory follow-up to determine the efficacy and security of the treatment. The investigators will measure all the laboratory variables related to the disease and possible adverse effects of the use of fibrates (creatine kinase, transaminases, bilirubin, alkaline phosphatase), also the investigators will measure the quality of life variables (pruritus severity, Short Form \[SF\]-36 questionnaire), and determine the fibrosis stage at the beginning and end of the study by non-invasive methods (transient elastography).

The study is directed to patients with PBC diagnosis who have had management with standard UDCA dose (13 to 15 mg/kg per day) for at least 6 months and had not reached complete biochemical response, defined by Paris II criteria. The dose of fibrate to use will be bezafibrate 200 mg every 12 hours or placebo every 12 hours for 12 months, both having the exact characteristics to avoid their recognition. Patients will continue the administration of UDCA at the same dose at enrollment. The intervention will be for a period of 12 months, with a follow-up every 3 months completing 5 medical follow-up visits (0, 3, 6, 9 and 12 months).

Conditions

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Primary Biliary Cirrhosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Bezafibrate & Ursodeoxycholic acid

Bezafibrate 200 mg capsule every 12 hours and ursodeoxycholic acid at a dose of 13 to 15 mg per Kg per day, for 12 months

Group Type EXPERIMENTAL

Bezafibrate

Intervention Type DRUG

Bezafibrate 200 mg manufactured in a pill/capsule presentation

Ursodeoxycholic Acid

Intervention Type DRUG

The patients will continue with the administration of ursodeoxycholic acid at a dose of 13 to 15 mg per Kg per day throughout the study

Placebo & Ursodeoxycholic acid

Placebo capsule (for bezafibrate 200 mg capsule) every 12 hours and ursodeoxycholic acid at a dose of 13 to 15 mg per Kg per day, for 12 months

Group Type PLACEBO_COMPARATOR

Ursodeoxycholic Acid

Intervention Type DRUG

The patients will continue with the administration of ursodeoxycholic acid at a dose of 13 to 15 mg per Kg per day throughout the study

Placebo (for Bezafibrate)

Intervention Type DRUG

Starch pill/capsule manufactured to mimic bezafibrate 200 mg tablet

Interventions

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Bezafibrate

Bezafibrate 200 mg manufactured in a pill/capsule presentation

Intervention Type DRUG

Ursodeoxycholic Acid

The patients will continue with the administration of ursodeoxycholic acid at a dose of 13 to 15 mg per Kg per day throughout the study

Intervention Type DRUG

Placebo (for Bezafibrate)

Starch pill/capsule manufactured to mimic bezafibrate 200 mg tablet

Intervention Type DRUG

Other Intervention Names

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Bezalip Ursofalk Does not apply

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role lead

Responsible Party

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Eric Lopez Mendez

Hepatologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Edgardo Eric Lopez Mendez, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Locations

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Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, , Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Edgardo Eric Lopez Mendez, MD

Role: CONTACT

(52)(55)54870900 ext. 2710

Sergio Gabriel Munoz Martinez, MD

Role: CONTACT

(52)(55)54870900 ext. 2710

Facility Contacts

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Edgardo Eric Lopez Mendez, MD

Role: primary

(01)(55) 54870900 ext. 2710

Sergio Gabriel Munoz Martinez, MD

Role: backup

(01)(55) 54870900 ext. 2710

References

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Related Links

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http://www.ingentaconnect.com/contentone/springer/hhci/2010/00000008/00000004/art00006

Krupp´s Fatigue Severity Scale taken from the article: Valencia-Flores, et al. Sleep, Fatigue, Depression, and Pain in Mexican Women with Systemic Lupus Erythematosus: An Exploratory Study. Hisp Health Care Int. 2010

Other Identifiers

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1757

Identifier Type: -

Identifier Source: org_study_id

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