Combination Antiretroviral Therapy (cART) for PBC
Randomized Controlled Trail (RCT) of Emtricitabine, Tenofovir Disoproxil and Raltegravir for Patients With Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid (UDCA)
1 other identifier
interventional
37
1 country
6
Brief Summary
Placebo Controlled, double-blind randomized controlled trial (RCT) with 12 months Tenofovir Disoproxil and Raltegravir for primary biliary cholangitis (PBC) patients unresponsive to Ursodeoxycholic Acid (UDCA). Placebo patients will be offered 12 months open label therapy at unblinding. All patients will be offered an additional 12 months open label therapy. Observational, open label study will be performed in parallel using Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) \& Raltegravir in liver transplant recipients meeting all entry criteria except for use of immunosuppression.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2021
Typical duration for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 7, 2019
CompletedFirst Posted
Study publicly available on registry
May 17, 2019
CompletedStudy Start
First participant enrolled
March 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2024
CompletedFebruary 16, 2024
February 1, 2024
1.6 years
May 7, 2019
February 15, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Change in alkaline phosphatase levels
Mean changes in alkaline phosphatase levels after 12 months treatment with combination antiretroviral therapy or placebo.
12 months
Secondary Outcomes (7)
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]
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]
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]
Achievement of the composite biochemistry endpoint
6 and 12 months
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
- +2 more secondary outcomes
Study Arms (2)
Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir
EXPERIMENTALone Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets
Placebo
PLACEBO COMPARATORIdentical tablets resembling one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets
Interventions
Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day
Raltegravir (RTF) 600 mg two tablets by mouth once per day
Two capsules identical to Raltegravir and one capsule identical to Truvada with no active ingredients by mouth once per day
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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/microL unless varices with risk of bleeding excluded by endoscopy within the last 6 months, 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Albertalead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (6)
University of Alberta
Edmonton, Alberta, T6G 2R3, Canada
St Paul's Hospital, University of British Columbia
Vancouver, British Columbia, V6Z 1Y6, Canada
Vancouver General Hospital, University of Brittish Columbia
Vancouver, British Columbia, V6Z 1Z4, Canada
University of Toronto
Toronto, Ontario, M5S 1A1, Canada
University of Montreal
Montreal, Quebec, Canada
Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew Mason, MD
University of Alberta
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double-blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 7, 2019
First Posted
May 17, 2019
Study Start
March 1, 2021
Primary Completion
October 1, 2022
Study Completion
January 1, 2024
Last Updated
February 16, 2024
Record last verified: 2024-02
Data Sharing
- IPD Sharing
- Will not share