Plain English Summary
Background and study aims
Hepatitis B is an infection of the liver caused by the hepatitis B virus (HBV). Nucleotide/nucleoside analogs are effective drugs for reducing the replication of HBV, but only a small percentage of patients are free of HBV infection (clearance) even after prolonged treatment. Hence, treatment is often continued for an indefinite period. Pegylated interferon alpha 2a (Peg IFN) is a drug that stimulates the immune system to attack HBV. The aims of this study are to find out whether adding Peg IFN to ongoing tenofovir treatment helps HBV patients to achieve infection clearance.
Who can participate?
Chronic HBV patients, aged over 18, who are taking tenofovir (a nucleotide analog)
What does the study involve?
Participants are randomly allocated to one of two groups. One group receives an injection of Peg IFN on a weekly basis for one year in addition to the tenofovir that they are already taking. The other group continue taking tenofovir on its own. Both groups of patients are regularly followed up for any side effects of the medication. Participants who achieve infection clearance eventually stop anti-viral treatment.
What are the possible benefits and risks of participating?
The benefit of Peg IFN is that more patients may achieve infection clearance, allowing them to stop anti-viral treatment. Achieving infection clearance with Tenofovir alone is unlikely, requiring the patient to pay for anti-viral treatment indefinitely. The most common side effects of Peg IFN are flu-like symptoms, tiredness, weakness, loss of appetite, skin reactions and insomnia. More serious side effects are hypothyroidism, worsening liver function and aggravation of autoimmune diseases, irritability, anxiety, depression and suicidal thoughts. Though these are known side effects, they are rare.
Where is the study run from?
King Faisal Specialist Hospital and Research Centre (Saudi Arabia)
When is the study starting and how long is it expected to run for?
April 2013 to February 2016
Who is funding the study?
King Faisal Specialist Hospital and Research Centre (Saudi Arabia)
Who is the main contact?
Dr Musthafa Peedikayil
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
-
Study information
Scientific title
HBsAg clearance in chronic hepatitis B patients with add-on pegylated interferon alpha 2a to ongoing tenofovir treatment: an open-label randomized controlled study
Acronym
Study hypothesis
By adding Peg IFN therapy to patients who already have the virological response with tenofovir will not increase the rate of hepatitis B surface antigen (HBsAg) clearance and or seroconversion in chronic hepatitis B patients.
Ethics approval
Ethics committee of King Faisal Specialist Hospital and Research Centre, 18/03/2013, ref: 2131012
Study design
Open-label prospective randomized controlled study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Chronic hepatitis B
Intervention
Patients with chronic hepatitis B (HBV) who were being treated with Tenofovir for more than six months and whose HBV DNA has been below 2000 IU/ml were eligible for recruitment. These patients were randomized into two groups. Random numbers were generated by a computer program.
Group A patients received pegylated interferon (Peg IFN) alpha 2a and tenofovir for one year followed by tenofovir indefinitely until they achieved study end point. Peg IFN alpha 2a was given at a dose of 180 mcg subcutaneously every week for a total of 48 weeks; these patients also continued Tenofovir 300 mg orally. The group A patients had clinic visits at week 2, week 4, week 12, week 24, week 36, and week 48; and then six monthly for one more year.
Group B patients were treated with tenofovir alone. Patients were seen every three months in the first year and then six monthly in the second year.
Patients in both groups received tenofovir 300 mg daily until they achieved HBsAg clearance or seroconversion. The duration of the study was for two years from the date of the first dose of peg IFN or day 1 of recruitment for patients in group B.
During each visit compliance, side effects of the drugs, and treatment response were assessed. Necessary laboratory and imaging studies were carried out before recruitment and while they were in the trial.
Intervention type
Drug
Phase
Not Applicable
Drug names
Pegylated interferon alpha 2a, tenofovir
Primary outcome measure
HBsAg clearance and development of anti-HBs antibodies, measured at regular periods before, during and after the trial period
Secondary outcome measures
Correlation between HBsAg clearance and HBsAg levels at different stages of the study period (pretreatment, on treatment and end of treatment HBsAg level)
Overall trial start date
16/04/2013
Overall trial end date
04/02/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female patients above 18 years of age
2. Chronic HBV patients receiving Tenofovir 300 mg orally daily for a minimum of 6 months
3. HBeAg-positive or HBeAg-negative patients
4. HBV DNA <2000 IU/ml before recruitment
5. HBsAg should be positive, and HBsAg titer should be measurable from the serum
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
50
Participant exclusion criteria
1. Side effects to medications or previous intolerance to Tenofovir or Peg IFN
2. Impaired renal function with a GFR <50
3. Hemoglobin <12 gm/L in women and <13 gm/L in men
4. Severe thrombocytopenia: platelets <75000
5. Neutropenia absolute neutrophil count (ANC)< 1000
6. Combined infection with HCV, HIV, HDV
7. Drug-induced, alcohol related or autoimmune liver disease
8. Patients with severe depression or other significant psychiatric illness
9. Previous history of lactic acidosis
10. Advanced cardiac, pulmonary, renal or neurological diseases
11. Liver cirrhosis with Child score (CTP) seven and above
12. Decompensated cirrhosis
13. Pregnancy and lactation
Recruitment start date
16/04/2013
Recruitment end date
04/02/2014
Locations
Countries of recruitment
Saudi Arabia
Trial participating centre
King Faisal Specialist Hospital and Research Centre
MBC 46
Department of Medicine
PO Box 3354
Riyadh
11211
Saudi Arabia
Sponsor information
Organisation
King Faisal Specialist Hospital and Research Centre
Sponsor details
MBC 46
Department of Medicine
PO Box 3354
Riyadh
11211
Saudi Arabia
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
King Faisal Specialist Hospital and Research Centre
Alternative name(s)
King Faisal Specialist Hospital
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
Saudi Arabia
Results and Publications
Publication and dissemination plan
Submitted the article for review
Intention to publish date
04/02/2017
Participant level data
Available on request
Basic results (scientific)
Publication list