A pilot study of Combivir® therapy for patients with primary biliary cirrhosis
| ISRCTN | ISRCTN22065123 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN22065123 |
| Secondary identifying numbers | N0265092544 |
- Submission date
- 12/09/2003
- Registration date
- 12/09/2003
- Last edited
- 15/11/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr JM Neuberger
Scientific
Scientific
Liver Medicine
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study objectives | This study will further test the hypothesis that there is an infectious aetiology involved in the development of primary biliary cirrhosis (PBC) by undertaking a randomised, controlled, phase II pilot study of Combivir® therapy in patients with PBC. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Primary biliary cirrhosis (PBC) |
| Intervention | This investigation is designed as a randomised, controlled, phase II pilot study of Combivir® in approximately 60 patients with PBC. It is expected that the majority of PBC patients will already be taking ursodeoxycholic acid and patients enrolled in the study will have been on this treatment for at least 6 months. Patients will be randomised to continue with ursodeoxycholic acid alone or in combination with Combivir®. The clinical, virological, histological and immune effects of the study drug will be examined. The clinical end point of the study will be 1 year of therapy or evidence for developing end stage liver disease. All PBC patients except for those with decompensated liver disease will be enrolled in the study after obtaining an informed written consent. The PBC patients will already be on ursodeoxycholic acid at an adjusted dose of 13 - 15 mg/kg of body weight/day in 2 - 3 divided doses. Patients treated with Combivir® will receive one tablet twice a day: Lamivudine 150 mg and Zidovudine 300 mg twice a day. Those patients not on ursodeoxycholic acid at the start of the study will be treated with ursodeoxycholic acid at the dose indicated for a period of 6 months prior to randomisation to ursodeoxycholic acid alone or in combination with Combivir® twice a day. At enrolment, each patient with PBC will be assessed for the inclusion criteria. Prior to therapy, patients will have a thorough history taken to assess symptoms. An objective graded clinical parameter scale will include the development, presence or worsening of pruritus, fatigue, sicca syndrome or right upper quadrant pain. At the same time patients will be examined for the presence or development of overt clinical signs such as jaundice, splenomegaly or hepatomegaly. At this point, the baseline blood tests will include: full blood count (FBC), reticulocyte count, prothrombin time (PT), erythrocyte sedimentation rate (ESR), blood urea nitrogen (BUN), creatinine, sodium, potassium, calcium, phosphate, albumin, total protein, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, creatine kinase (CK), amylase, immunoglobulins, antinuclear antibodies (ANA), and quantitated AMA. All of these are laboratory assessments that are clinically useful in following patients with PBC. Unless problems develop in the interim, patients will be seen at months 1, 3, 6, 9 and 12 after initiation of therapy. At the initial clinic visit, blood will be drawn for BUN, creatinine, electrolytes, amylase, bilirubin, AST, ALT, alkaline phosphatase, albumin, PT, serum lactate and FBC. Subsequently, samples will be drawn for hepatic biochemistry, as well as virological and immunological studies. Patients will undergo a physical exam at each visit and also be questioned about changes in symptoms. Liver biopsies will be performed as clinically indicated. Response to therapy will be based on changes in symptomatology, development of overt clinical signs, immunological parameters, improvement of liver function and biochemistry. Immunological studies include quantitative AMA levels. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot virological studies will be performed on serum samples before and after therapy in the Hepatitis Research Laboratory, Alton Ochsner Medical Foundation, USA. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Ursodeoxycholic acid, Combivir® (lamivudine and zidovudine) |
| Primary outcome measure | Not provided at time of registration |
| Secondary outcome measures | Not provided at time of registration |
| Overall study start date | 01/10/2001 |
| Completion date | 01/05/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 60 |
| Key inclusion criteria | Patients will be recruited from the Liver Out-Patients Department at the Queen Elizabeth Hospital: 1. Patients greater than 20 years old of either sex 2. Elevated alkaline phosphatase or alanine aminotransferase (ALT) within 3 months prior to the start of therapy 3. Positive serum anti-mitochondrial antibodies (AMA) (titre greater than 1:20) 4. Liver biopsy histology compatible with PBC |
| Key exclusion criteria | 1. Patients treated with immunosuppressive or anti-inflammatory agents 2. Advance liver disease: Child's class B or C 3. Patients with secondary hepatological diagnosis 4. Alcohol abuse (greater than 50 g of alcohol per day) 5. Other significant co-morbidity (e.g. cardiac or renal failure) 6. Pregnancy or breast feeding 7. Sexually active female of child bearing age not using effective contraception |
| Date of first enrolment | 01/10/2001 |
| Date of final enrolment | 01/05/2005 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Liver Medicine
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Sponsor information
Department of Health (UK)
Government
Government
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
| Website | http://www.doh.gov.uk |
|---|
Funders
Funder type
Industry
University Hospital Birmingham NHS Trust (UK)
No information available
NHS R&D Support Funding
No information available
GlaxoSmithKline (GSK) (UK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/12/2004 | Yes | No |
