A pilot study of Combivir® therapy for patients with primary biliary cirrhosis

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN22065123
• Date of registration: 12/09/2003
• Prospective Registration: No
• Primary sponsor: Record provided by the NHS Trusts Clinical Trials Register - Department of Health (UK)
• Public title: A pilot study of Combivir® therapy for patients with primary biliary cirrhosis
• Date of first enrolment: 01/10/2001
• Target sample size: 60
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN22065123
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)

Countries of recruitment

United Kingdom

Contacts

• Name: JM Neuberger

Key inclusion & exclusion criteria

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
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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Primary biliary cirrhosis (PBC)
Digestive System
Fibrosis and cirrhosis of liver

Intervention(s)

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, phosph

Primary Outcome(s)

Not provided at time of registration

Secondary Outcome(s)

Not provided at time of registration

Secondary ID(s)

N0265092544

Source(s) of Monetary Support

University Hospital Birmingham NHS Trust (UK), NHS R&D Support Funding, GlaxoSmithKline (GSK) (UK)