Health benefits from anti-viral therapy for mild chronic hepatitis C

ISRCTN ISRCTN24461054
DOI https://doi.org/10.1186/ISRCTN24461054
Secondary identifying numbers HTA 95/24/03
Submission date
25/04/2003
Registration date
25/04/2003
Last edited
08/11/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Howard Thomas
Scientific

Department of Medicine
St Mary's Hospital
Imperial College School of Medicine at St Mary's
10th Floor QEQM Wing
South Wharf Road
London
W2 1PG
United Kingdom

Phone +44 (0)20 7886 6454
Email h.thomas@imperial.ac.uk

Study information

Study designMulticentre, randomised, controlled, non-blinded trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeNot Specified
Scientific titleHealth benefits from anti-viral therapy for mild chronic hepatitis C
Study objectivesA multicentre, randomised study comparing interferon and ribavarin with no treatment for patients with mild chronic Hepatitis C.
Ethics approval(s)Added as of 23/07/2007: Ethics committee approval was obtained both centrally (MREC/98/2/12) and from each Local Centre Committee (LREC).
Health condition(s) or problem(s) studiedInfection and infestations: Hepatitis
InterventionPlease note that, as of 14 January 2008, the anticipated end date of this trial has been updated from 31 July 2001 to 31 October 2003.

Interventions:
1. Interferon and ribavarin
2. No treatment
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Interferon and ribavarin
Primary outcome measurePrimary outcome measure updated as of 24/07/2007:
Sustained Virological Response (SVR) at 24 weeks post-treatment.

Primary outcome measure provided at time of registration:
Analysis includes health economics, quality of life and virological end points.
Secondary outcome measuresSecondary outcome measures added as of 24/07/2007:
1. Baseline factors predicting SVR
2. Changes in histopathology
3. Health-Related Quality of Life (HRQoL)
4. Viral kinetics: the relationship of early viral kinetics to final treatment outcome
5. Adverse events
Overall study start date01/08/1998
Completion date31/10/2003

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants204
Key inclusion criteriaInclusion criteria updated as of 24/07/2007:
1. Adult, male or female, minimum age of 18 years
2. Serum positive for HCV by quantitative Polymerase Chain Reaction (qPCR) assay
3. Liver biopsy within 1 year before entry to the protocol. Histological diagnosis consistent with mild chronic hepatitis (Ishak necroinflammatory score <4, fibrosis score <3)
4. Compensated liver disease with the following minimum haematological, biochemical and serological criteria at the screening visit:
4.1. Haemoglobin (Hb) ≥12 g dl–1 for women and ≥13 g dl–1 for men
4.2. White Blood Cell count (WBC) ≥ 3000 mm–3
4.3. Granulocyte count ≥1500 mm–3
4.4. Platelets ≥100,000 mm–3
4.5. Prothrombin time/ International Normalised Ratio (INR) within normal limits
4.6. Bilirubin within normal limits (unless non-hepatitis-related factors such as Gilbert’s disease explain a rise)
4.7. Albumin stable and within normal limits
4.8. Serum creatinine within normal limits
4.9. Fasting blood sugar within normal limits for non-diabetic patients
4.10. Glycosylated haemoglobin (HbA1c) <8.5% for diabetic patients (whether diet controlled or on medication)
4.11. TSH within normal limits (patients requiring medication to maintain Thyroid-Stimulating Hormone (TSH) levels in the normal range were eligible if all other inclusion/exclusion criteria were met)
4.12. AntiNuclear Antibodies (ANA) <1:160
4.13. Anti-HIV antibody negative
4.14. Serum hepatitis B surface antigen (HBsAg) negative
5. Confirmation and documentation that sexually active patients of childbearing potential were practising adequate contraception during the treatment period and for 6 months after discontinuation of therapy. A serum pregnancy test was obtained at entry before the initiation of treatment and had to be negative. Female patients could not breast-feed.

Inclusion criteria provided at time of registration:
Patients with hepatitis C
Key exclusion criteriaExclusion criteria added as of 24/07/2007:
1. Prior treatment with interferon-alpha or ribavirin
2. Hypersensitivity to interferon-alpha or ribavirin
3. Participation in any other clinical trial within 30 days of entry to this protocol
4. Treatment with any investigational drug within 30 days of entry to this protocol
5. Prior treatment for hepatitis with any other antiviral or immunomodulatory drug within the previous 2 years
6. Any other cause for the liver disease other than chronic hepatitis C, including but not limited to:
6.1. Coinfection with hepatitis B virus
6.2. Haemochromatosis (iron deposition >2+ in liver parenchyma)
6.3. Alpha1-antitrypsin deficiency
6.4. Wilson’s disease
6.5. Autoimmune hepatitis
6.6. Alcoholic liver disease
6.7. Obesity-induced liver disease
6.8. Drug-related liver disease
7. Haemophilia or any other condition preventing the patient from having a liver biopsy, including anticoagulant therapy
8. Haemoglobinopathies (e.g. thalassaemia)
9. Evidence of advanced liver disease, such as history or presence of ascites, bleeding varices, encephalopathy
10. Patients with organ transplants
11. Any known pre-existing medical condition that could interfere with the patient’s participation in and completion of the
protocol such as:
11.1. Pre-existing psychiatric condition (e.g. severe depression, or a history of severe psychiatric disorder)
11.2. CNS trauma or seizure disorder requiring medication
11.3. Significant cardiovascular dysfunction within the past 6 months (e.g. angina, congestive cardiac failure, recent myocardial infarction, severe hypertension or significant arrhythmia)
11.4. Patients with an ECG showing clinically significant abnormalities
11.5. Poorly controlled diabetes mellitus
11.6. Chronic pulmonary disease (e.g. chronic obstructive pulmonary disease)
11.7. Immunologically mediated disease (e.g. inflammatory bowel disease, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, cryoglobulinaemia with vasculitis)
11.8. Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids
11.9. Gout
12. Substance abuse, such as excessive alcohol intake (>50 g day–1) or erratic use of intravenous or inhaled drugs
13. Patients with clinically significant retinal abnormalities
14. Any other condition which in the opinion of the investigator would make the patient unsuitable for enrolment or that could interfere with the patient participating in or completing the protocol
Date of first enrolment01/08/1998
Date of final enrolment31/10/2003

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Department of Medicine
London
W2 1PG
United Kingdom

Sponsor information

Department of Health (UK)
Government

Quarry House
Quarry Hill
Leeds
LS2 7UE
United Kingdom

Phone +44 (0)1132 545 843
Email Sheila.Greener@doh.gsi.gov.uk
Website http://www.dh.gov.uk/en/index.htm
ROR logo "ROR" https://ror.org/03sbpja79

Funders

Funder type

Government

NIHR Health Technology Assessment Programme - HTA (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article HTA monograph 01/07/2006 Yes No

Editorial Notes

08/11/2022: Internal review.