Rituximab for the treatment of fatigue in primary biliary cirrhosis
- Conditions
- Oral and gastrointestinal, hepatologyDigestive SystemPrimary biliary cirrhosis
- Registration Number
- ISRCTN03978701
- Lead Sponsor
- ewcastle upon Tyne Hospitals NHS Foundation Trust (UK)
- Brief Summary
1. 2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26297361 2. 2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29733563
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 58
1. Age 18 years or over
2. Patient has capacity and provided written informed consent for participation in the study prior to any study specific procedures
3. Moderate or severe fatigue as assessed using previously designated cut-offs of the PBC-40 fatigue domain (i.e. fatigue domain score >33)
4. Presence of AMA (anti-PDH antibody) at a titre of >1:40
5. Adequate haematological function Hb >9g/L, absolute neutrophil count >1.5x109/L, platelet count > 50x109/L
6. Bilirubin = 50 µmol
7. INR = 1.5
8. Child-Pugh score < 7
9. ECOG performance status < 2
10. Adequate renal function Cockroft and Gault estimation > 40ml/min
11. Women of childbearing potential should have a negative pregnancy test prior to study entry AND be using an adequate contraception method, which must be continued for 3 months after completion of treatment
12. Male & female participants
1. Advanced or decompensated disease (variceal bleed, hepatic encephalopathy or ascites)
2. History or presence of other concomitant liver diseases (including hepatitis due to hepatitis B or C or evidence of chronic viraemia on baseline screening), primary sclerosing cholangitis or biopsy proven non-alcoholic steatohepatitis)
3. Average alcohol ingestion >21 units/week (male) or >14 units / week (female)
4. Chronic sepsis or intercurrent condition likely to predispose to chronic sepsis during the study
5. Previous treatment with B-cell depleting therapy
6. Previous history of aberrant response or intolerance to immunological agents
7. Presence of significant untreated intercurrent medical condition itself associated with fatigue
8. Presence of significant risk of depressive illness (HADS score indicating caseness)
9. Current statin therapy or statin use within 3 months of enrolment
10. Ongoing participation in other clinical trials or exposure to any investigational agent 4 weeks prior to baseline or within <5 half lives of the investigational drug
11. Major surgery within 4 weeks of trial entry
12. Vaccination within 4 weeks of trial entry, patients requiring seasonal flu or travel vaccines will be required to wait a minimum of 4 weeks post vaccination to enroll in the trial
13. Pregnant or lactating women
14. Psychiatric or other disorder likely to impact on informed consent
15. Patient is unable and/or unwilling to comply with treatment and study instructions
16. Any other medical condition that, in the opinion of the investigator would interfere with safe completion of the trial
17. Hypersensitivity to the active substance (Rituximab) or to any of the excipients (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water (for infusion)) or to murine proteins
18. Active, severe infections (e.g. tuberculosis, sepsis or opportunistic infections)
19. Known HIV infection
20 .Clinical history of Latent TB infection unless the patient has completed adequate antibiotic prophylaxis
21. AST/ALT 4 x Upper Limit of Normal
22. Severe immune-compromised state
23. Severe heart failure (NYHA Class IV) or severe uncontrolled cardiac disease
24. Malignancy (other than basal cell carcinoma) within the last 10 years
25. Demyelinating disease
26. Previous participation in this trial
27. Any contraindication to Rituximab therapy not covered by other exclusions
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Fatigue severity in PBC patients and quality of life measured at baseline, 12 weeks, and three monthly thereafter up to 12 months
- Secondary Outcome Measures
Name Time Method