Use of Bezafibrate in Patients With Primary Biliary Cirrhosis to Archive Complete Biochemical Response in Non-responders
Ключови думи
Резюме
Описание
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).
Дати
| Последна проверка: | 03/31/2018 |
| Първо изпратено: | 10/12/2016 |
| Очаквано записване подадено: | 10/13/2016 |
| Първо публикувано: | 10/17/2016 |
| Изпратена последна актуализация: | 04/18/2018 |
| Последна актуализация публикувана: | 04/22/2018 |
| Действителна начална дата на проучването: | 09/30/2016 |
| Приблизителна дата на първично завършване: | 03/31/2019 |
| Очаквана дата на завършване на проучването: | 11/30/2019 |
Състояние или заболяване
Интервенция / лечение
Drug: Bezafibrate & Ursodeoxycholic acid
Drug: Ursodeoxycholic Acid
Drug: Placebo & Ursodeoxycholic acid
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| 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 & Ursodeoxycholic acid Bezafibrate 200 mg manufactured in a pill/capsule presentation |
| 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: Placebo & Ursodeoxycholic acid Starch pill/capsule manufactured to mimic bezafibrate 200 mg tablet |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | 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 |
Резултат
Първични изходни мерки
1. Complete biochemical response [12 months]
Вторични изходни мерки
1. Increase in liver transaminases or development of rhabdomyolysis [Follow-up every 3 months for 12 months.]
Други изходни мерки
1. Comparison of fatigue between groups [Two evaluations: At enrollment and 12 months later.]
2. Quality of life [Two evaluations: At enrollment and 12 months later.]
3. Pruritus intensity [Follow-up every 3 months for 12 months.]
4. Liver fibrosis evaluation by a non-invasive method [Two evaluations: At enrollment and 12 months later.]
5. Disease natural history outcome [Two evaluations: At enrollment and 12 months later.]
6. Prognostic scales comparison [Two evaluations: At enrollment and 12 months later.]
