ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02937012
Recruitment Status : Recruiting
First Posted : October 18, 2016
Last Update Posted : April 23, 2018
Sponsor:
Information provided by (Responsible Party):
Eric Lopez Mendez, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Brief 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?


Condition or disease Intervention/treatment Phase
Primary Biliary Cirrhosis Drug: Bezafibrate Drug: Ursodeoxycholic Acid Drug: Placebo (for Bezafibrate) Phase 3

Detailed Description:

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).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Security of Bezafibrate in Patients With Primary Biliary Cirrhosis Without Biochemical Response to Ursodeoxycholic Acid: A Randomized, Double-blind, Placebo-controlled Trial
Study Start Date : October 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: 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
Drug: Bezafibrate
Bezafibrate 200 mg manufactured in a pill/capsule presentation
Other Name: Bezalip
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
Other Name: Ursofalk
Placebo Comparator: 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
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
Other Name: Ursofalk
Drug: Placebo (for Bezafibrate)
Starch pill/capsule manufactured to mimic bezafibrate 200 mg tablet
Other Name: Does not apply



Primary Outcome Measures :
  1. Complete biochemical response [ Time Frame: 12 months ]
    The complete biochemical response in patients with primary biliary cholangitis is defined as the reduction of alkaline phosphatase lower than 1.5 times the upper normal limit, reduction of aspartate transaminase lower than 1.5 times the upper normal limit and bilirubin lower than 1 mg/dL


Secondary Outcome Measures :
  1. Increase in liver transaminases or development of rhabdomyolysis [ Time Frame: Follow-up every 3 months for 12 months. ]
    Elevation of transaminases of biochemical evidence of rhabdomyolysis.


Other Outcome Measures:
  1. Comparison of fatigue between groups [ Time Frame: Two evaluations: At enrollment and 12 months later. ]
    Clinical evaluation of fatigue with the use of the Krupp´s Fatigue Severity Scale.

  2. Quality of life [ Time Frame: Two evaluations: At enrollment and 12 months later. ]
    Evaluation of the quality of life with the SF-36 questionnaire.

  3. Pruritus intensity [ Time Frame: Follow-up every 3 months for 12 months. ]
    Evaluation made by the use of visual analogue scales.

  4. Liver fibrosis evaluation by a non-invasive method [ Time Frame: Two evaluations: At enrollment and 12 months later. ]
    Evaluation of the liver fibrosis by transient elastography.

  5. Disease natural history outcome [ Time Frame: Two evaluations: At enrollment and 12 months later. ]
    Compare the liver transplant-free survival, overall survival and liver decompensation-free survival between groups.

  6. Prognostic scales comparison [ Time Frame: Two evaluations: At enrollment and 12 months later. ]
    Compare the different prognostic scales (Mayo, Child-Pugh and MELD) between groups.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02937012


Contacts
Contact: Edgardo Eric Lopez Mendez, MD (52)(55)54870900 ext 2710 ericlopezmendez@yahoo.com.mx
Contact: Sergio Gabriel Munoz Martinez, MD (52)(55)54870900 ext 2710 sergio_sg@hotmail.com

Locations
Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Recruiting
Mexico City, Mexico, 14000
Contact: Edgardo Eric Lopez Mendez, MD    (01)(55) 54870900 ext 2710    ericlopezmendez@yahoo.com.mx   
Contact: Sergio Gabriel Munoz Martinez, MD    (01)(55) 54870900 ext 2710    sergio_sg@hotmail.com   
Principal Investigator: Edgardo Eric Lopez Martinez, MD         
Sub-Investigator: Sergio Gabriel Munoz Martinez, MD         
Sub-Investigator: Ignacio Garcia Juarez, MD         
Sub-Investigator: Ernesto Marquez Guillen, MD         
Sub-Investigator: Carlos Moctezuma Velazquez, MD         
Sub-Investigator: Alejandra Tepox Padron, MD         
Sponsors and Collaborators
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Investigators
Principal Investigator: Edgardo Eric Lopez Mendez, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Additional Information:
Publications of Results:

Responsible Party: Eric Lopez Mendez, Hepatologist, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
ClinicalTrials.gov Identifier: NCT02937012     History of Changes
Other Study ID Numbers: 1757
First Posted: October 18, 2016    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Eric Lopez Mendez, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:
Primary Biliary Cirrhosis
Primary Biliary Cholangitis
Bezafibrate
Ursodeoxycholic acid

Additional relevant MeSH terms:
Ursodeoxycholic Acid
Fibrosis
Liver Cirrhosis
Liver Cirrhosis, Biliary
Pathologic Processes
Liver Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Bezafibrate
Cholagogues and Choleretics
Gastrointestinal Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents