A multicenter randomised study comparing the efficacy of adefovir dipivoxil versus pegylated interferon alpha-2a plus placebo versus adefovir dipivoxil plus peglyated interferon alpha-2a for the treatment of chronic delta hepatitis

ISRCTN	ISRCTN83587695
DOI	https://doi.org/10.1186/ISRCTN83587695
Protocol serial number	3388
Sponsor	Hannover Medical School (MHH) (Germany)
Funder	Network of competence for hepatitis (Kompetenznetz Hepatitis [Hep-Net e.V.]), c/o Hannover Medical School (Medizinische Hochschule Hannover [MHH]) (Germany)

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Prof Michael P Manns
Scientific

Medizinische Hochschule Hannover
Department for Gastroenterology, Hepatology and Endocrinology
Carl-Neuberg-Str. 1
Hannover
30625
Germany

Phone	+49 5115323306
Email	manns.michael@mh-hannover.de

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	Delta Study
Study objectives	Peg-interferon alpha-2a or adefovir lead to sustained virological response in 20-40% of the cases in chronic delta hepatitis.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Adults with chronic delta hepatitis
Intervention	A: Adefovir dipivoxil, 10 mg, orally (po) for 48 weeks versus B: Pegylated interferon alpha-2a, 180 µg subcutaneously (sc), plus placebo for 48 weeks versus C: Pegylated interferon alpha-2a, 180 µg sc, plus adefovir dipivoxil, 10 mg po for 48 weeks; biopsy at the end of treatment
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Peg-interferon alpha-2a, adefovir dipivoxil
Primary outcome measure(s)	Response rate of normal ALT and HDV RNA negativity at the end of treatment (ETR)
Key secondary outcome measure(s)	1. Response rate of normal ALT and HDV RNA negativity at the end of follow-up (EOF) 2. Suppression of hepatitis B virus (HBV) DNA below 1x10^5 copies/ml at ETR and EOF 3. Paired biopsy comparison 4. HBsAg levels, loss of HBsAg and HBs Antibodies at ETR and EOF 5. HBV and HDV specific T cell response 6. Saftey (adverse events, vital signs, clinical laboratory parameters)
Completion date	01/10/2004

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	69
Key inclusion criteria	1. Age >18 years 2. Positive Hepatits B surface Antigen (HBsAg) 3. Positive anti-hepatitis D virus (HDV) antibodies 4. Positive HDV-Ribonucleic Acid (RNA) by Polymerase Chain Reaction (PCR) 5. Serum alanine aminotransferase (ALT) >upper limit of normal (ULN) but <10 x ULN 6. Liver biopsy demonstrating liver disease consistent with chronic heaptitis 7. Liver imaging for patients with cirrhosis or marked fibrosis to rule out hepatic carcinoma 8. Negative urine or serum pregnancy test 9. Willingness to give written informed consent
Key exclusion criteria	1. Antiviral therapy in previous six months 2. Positive tests for hepatitis A virus (HAV) Immunoglobulin M (IgM) antibodies, hepatitis C virus (HCV) RNA or HCV antibodies or Human Immunodeficiency Virus (HIV) antibodies 3. Serum total bilirubin >2 x ULN 4. Decompensated liver disease Child B-C 5. Other reasons for chronic liver disease 6. Haemoglobin <11.5 g/dl for females and <12.5 g/dl for males 7. White blood cell count (WBC) <3000 cells/mm^3 8. Serum creatinine >1.5 x ULN 9. Relevant psychiatric diseases 10. Drug or alcohol abuse within one year of entry 11. Other evidence or histroy of severe illness 12. Thyroid disease poorly controlled 13. Alphafetoprotein (AFP) >100 ng/ml
Date of first enrolment	01/04/2004
Date of final enrolment	01/10/2004

Medizinische Hochschule Hannover

Hannover
30625
Germany

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	27/01/2011		Yes	No