Combination Antiretroviral Therapy (cART) for PBC
Ключови думи
Резюме
Описание
Primary endpoint:
Greater than 10% difference in mean percentage of alkaline phosphatase (ALP) reduction in cART vs. placebo at 6 and 12 months.
Secondary endpoints:
1. Serum biochemistries bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) will be studied as continuous variables.
2. Composite endpoint used for the POISE study [A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis]: (i) reduction of ALP to < 1.67 upper limit of normal, (ii) normalization of bilirubin within upper limit of normal (ULN) and (iii) reduction of ALP by > 15% at 6 and 12 months.
3. Symptomatic evaluation performed using the PBC-40 to assess five symptom domains relating to fatigue, itch, cognitive symptoms, social and emotional symptoms, and other symptoms.
4. Histological change in grade and stage of PBC using the Nakanuma scoring system for a subgroup of patients undergoing liver biopsy [liver biopsy not compulsory for study].
5. Serial human betaretrovirus measurement in peripheral blood and cellular immune response to viral peptides.
Дати
| Последна проверка: | 02/29/2020 |
| Първо изпратено: | 05/06/2019 |
| Очаквано записване подадено: | 05/15/2019 |
| Първо публикувано: | 05/16/2019 |
| Изпратена последна актуализация: | 03/26/2020 |
| Последна актуализация публикувана: | 03/30/2020 |
| Действителна начална дата на проучването: | 08/31/2020 |
| Приблизителна дата на първично завършване: | 10/31/2022 |
| Очаквана дата на завършване на проучването: | 10/31/2023 |
Състояние или заболяване
Интервенция / лечение
Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir
Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir
Drug: Placebo
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Experimental: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir | Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day |
| Placebo Comparator: Placebo | Drug: Placebo Two capsules identical to Raltegravir and one capsule identical to Truvada with no active ingredients by mouth once per day |
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: - over 18 years old of either sex, - Anti-mitochondrial antibody +ve or liver histology compatible with PBC, - stable UDCA dose of 13-15 mg/kg for > 12 months or intolerant to UDCA, - ALP at least 1.67 x ULN or abnormal bilirubin less than 2x ULN - able to read and sign informed consent form. Exclusion Criteria: - subjects with baseline total bilirubin > 2 x ULN, - use of non-standard or experimental therapy within the last 6 months, - advanced liver disease: INR > 1.2 ULN, Albumin < 35 g/L lower limit of normal, platelets < 120,000, Childs Pugh class B or C cirrhosis, presence of grade 2 varices or previous variceal hemorrhage, encephalopathy, ascites or need for liver transplantation within the next two years; - secondary diagnosis such as HIV, viral hepatitis, drug induced liver injury, extrahepatic biliary obstruction, primary sclerosing cholangitis, metabolic liver - regular use of > 30g alcohol/day in the last year; - a predicted survival of less than 3 years from malignant or other life threatening disease; - hepatic mass consistent with hepatocellular carcinoma ; - previous allergic reaction to study medications; - Glomerular Filtration Rate less than < 30 mL/min as measured Cockcroft-Gault formula; - pregnancy, breast-feeding or pre-menopausal patients not using contraception. |
Резултат
Първични изходни мерки
1. Change in alkaline phosphatase levels [12 months]
Вторични изходни мерки
1. Serial changes in alkaline phosphatase [Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy]]
2. Serial changes in ALT [Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy]]
3. Serial changes in bilirubin [Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy]]
4. Achievement of the composite biochemistry endpoint [6 and 12 months]
5. Human Betaretrovirus load in peripheral blood [Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy]
6. Interferon gamma release to Human Betaretrovirus peptide stimulation [Evaluation at baseline, 6 months and end of RCT; then 6 monthly to end of open label therapy]
7. Liver histology [Pretreatment biopsy and 24 month biopsy after initiation of study therapy]
