HBsAg clearance with pegylated interferon and tenofovir combination

ISRCTN ISRCTN12811193
DOI https://doi.org/10.1186/ISRCTN12811193
Submission date
20/08/2016
Registration date
26/08/2016
Last edited
24/08/2016
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

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

Contact information

Dr Musthafa Peedikayil
Scientific

Department of Medicine
MBC 46
PO Box 3354
Riyadh
11211
Saudi Arabia

Study information

Study designOpen-label prospective randomized controlled study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleHBsAg clearance in chronic hepatitis B patients with add-on pegylated interferon alpha 2a to ongoing tenofovir treatment: an open-label randomized controlled study
Study objectivesBy 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(s)Ethics committee of King Faisal Specialist Hospital and Research Centre, 18/03/2013, ref: 2131012
Health condition(s) or problem(s) studiedChronic hepatitis B
InterventionPatients 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Pegylated interferon alpha 2a, tenofovir
Primary outcome measureHBsAg clearance and development of anti-HBs antibodies, measured at regular periods before, during and after the trial period
Secondary outcome measuresCorrelation between HBsAg clearance and HBsAg levels at different stages of the study period (pretreatment, on treatment and end of treatment HBsAg level)
Overall study start date16/04/2013
Completion date04/02/2016

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants50
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment16/04/2013
Date of final enrolment04/02/2014

Locations

Countries of recruitment

  • Saudi Arabia

Study participating centre

King Faisal Specialist Hospital and Research Centre
MBC 46
Department of Medicine
PO Box 3354
Riyadh
11211
Saudi Arabia

Sponsor information

King Faisal Specialist Hospital and Research Centre
Hospital/treatment centre

MBC 46
Department of Medicine
PO Box 3354
Riyadh
11211
Saudi Arabia

Website http://www.kfshrc.edu.sa/en/home
ROR logo "ROR" https://ror.org/05n0wgt02

Funders

Funder type

Hospital/treatment centre

King Faisal Specialist Hospital and Research Centre
Private sector organisation / Other non-profit organizations
Alternative name(s)
King Faisal Specialist Hospital
Location
Saudi Arabia

Results and Publications

Intention to publish date04/02/2017
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planSubmitted the article for review
IPD sharing plan