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Prednisolone Priming Study in Patients With Chronic Hepatitis B
This study is ongoing, but not recruiting participants.
First Received: October 21, 2008   Last Updated: November 12, 2008   History of Changes
Sponsored by: Chang Gung Memorial Hospital
Information provided by: Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT00778596
  Purpose

Study purpose:

To investigate whether ALT rebound following corticosteroid priming enhances response to telbivudine therapy.

Efficacy assessments:

The primary endpoint will be the 1-year HBe-Ag seroconversion rate with or without prednisolone priming.

Data analysis:

A summary table will be presented as frequency tables for categorical variables as number, and percentage, whereas descriptive tables for continuous variables as number, mean ± SD and median (minimum, maximum). All statistical assessments will be two-sided and evaluated at significance level of 0.05.

Continuous variables will be analyzed using t-test, or ANOVA, and categorical variables will be analyzed using chi-square or Fisher's exact test. A non-parametric method, Wilcoxon rank-sum or sign-rank tests will be conducted for continuous, and categorical variables if data is far from normal distribution.


Condition Intervention Phase
Chronic Hepatitis B
Drug: Prednisolone
Drug: Placebo priming
Phase IV

MedlinePlus related topics: Hepatitis Hepatitis B
Drug Information available for: Prednisolone Prednisolone acetate Depo-medrol Medrol veriderm Methylprednisolone Hepatitis B Vaccines Prednisolone sodium phosphate Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate Telbivudine 6-Methylprednisolone
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title: A Randomized, Double Blind Controlled Trial to Evaluate the Therapeutic Effect of Telbivudine With or Without Prednisolone Priming in Patients With Chronic Hepatitis B

Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • The primary endpoint will be the 1-year HBe-Ag seroconversion rate with or without prednisolone priming. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: October 2008
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Prednisolone priming: Experimental
Prednisolone priming 4 weeks, then treated with telbivudine.
Drug: Prednisolone
Prednisolone priming for 4 weeks, then followed a telbivudine treatment for 2 years.
Placebo priming: Placebo Comparator
Placebo priming for 4 weeks, then followed a telbivudine treatment for 2 years.
Drug: Placebo priming
Prednisolone priming for 4 weeks, then followed a telbivudine treatment for 2 years.

Detailed Description:

This is a Phase IV, multi-center, double-blinded, placebo control randomized study to evaluate the therapeutic effect of telbivudine with or without prednisolone priming in patients with chronic hepatitis B.

Patients are allocated to either group A or B randomly.

Group A: Patients initially receive a 4-week course of oral prednisolone (30 mg daily for 3 weeks and then 15 mg daily of 1 week). After a rest period of no treatment for 2 weeks, the patients receive telbivudine therapy at a daily dose of 600 mg for 2 years. Patients will be asked to come back to clinic for follow-up 6 months after telbivudine treatment.

Group B: Patients receive a 4-week course of placebo. After a rest period of no treatment for 2 weeks, the patients receive telbivudine therapy at a daily dose of 600 mg for 2 years. Patients will be asked to come back to clinic for follow-up 6 months after telbivudine treatment.

Eligible patients will be randomized prior to the first dose of study medication. The visit at which the patient receives the first dose will be defined as the study Baseline. Patients will return to the clinic at 3, 4, 6, 10, 14, 18, 30, 44, 58, 72, 86, 98, 110, 116, 122, 128 and 134 weeks post-Baseline.

At each of these visits, routine clinical laboratory tests, adverse event inquiry, and other clinical assessments will be performed. Serum samples for HBV DNA analysis will be obtained at 4, 6, 30, 58, 86, 110 and 134 weeks. Serum samples for HBV sequencing will be obtained at Screening and Week 110 (or upon early termination from the study).

Complete physical examinations will be performed at each study visits to evaluate any adverse signs or symptoms reported by the patient.

Serum for HBeAg, antibody to HBeAg (HBeAb), HBsAg, and antibody to HBsAg (HBsAb) will be obtained at Screening, Baseline, and Weeks 6, 30, 58, 86, 110 and 134(or upon early termination from the study), and at all protocol-required follow-up visits.

Patients will be followed monthly for 6 months after discontinuation of study drug(s).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Treatment naïve patients or interferon-treated patients 6 months before.
  2. Male or female, 18 to 65 years of age.
  3. Documented chronic hepatitis B defined by all of the following:

    • Clinical history compatible with compensated chronic hepatitis B.
    • Detectable serum hepatitis B surface antigen (HBsAg) >6 months and at the screening visit.
    • Hepatitis B e antigen (HBeAg) positive >3 months.
    • Serum HBV DNA > 2x105 IU/mL and raised serum ALT > 2xULN but < 5xULN determined on at least 2 occasions 1 month apart before.
  4. Liver biopsy showing chronic hepatitis and fibrosis stage ≦ 4 by Ishak classification within 6 months.
  5. Willing and able to comply with the study drug regimen and all other study requirements.
  6. Willing and able to provide written informed consent to participate in the study.

Exclusion Criteria:

Patients will be excluded from the study for any of the following reasons:

  1. Pregnant or nursing.
  2. Of reproductive potential (men and women) and unwilling to use double-barrier method of contraception (i.e., condom with spermicide or diaphragm with spermicide).
  3. Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV.
  4. History or clinical signs/symptoms of hepatic decompensation or portal hypertension, such as ascites, presence of esophageal varices or variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis.
  5. Liver cirrhosis (Ishak fibrosis score 5 or 6).
  6. Any medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir (e.g., for recurrent herpes virus infections).
  7. History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha-fetoprotein (AFP) levels. A history of treated malignancy other than HCC is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding 3 years.
  8. One or more known primary or secondary causes of liver disease other than hepatitis B (e.g., alcoholism, non-alcoholic steatohepatitis, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease). Gilbert's syndrome and Dubin-Johnson syndrome will not exclude patients from participation in this trial.
  9. History of clinically evident pancreatitis.
  10. Currently abusing alcohol (i.e., an average daily intake of more than 40 g of ethanol) or illicit drugs or a history of alcohol abuse or illicit substance abuse within the preceding 2 years. Patients currently on methadone maintenance treatment programs are NOT eligible.
  11. A medical condition that requires frequent or prolonged use of systemic corticosteroids (e.g., severe asthma, severe arthritis or autoimmune conditions, organ transplantation, adrenal insufficiency).
  12. A medical condition requiring the chronic or prolonged use of potentially hepatotoxic drugs (dapsone, erythromycin, fluconazole, ketoconazole, rifampin, anti-tuberculosis regimens, etc.). All such drugs must have been discontinued ≥ 30 days prior to randomization.
  13. A medical condition requiring use of nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, foscarnet, vancomycin, cyclosporine, tacrolimus, or frequent nonsteroidal anti-inflammatory drugs (NSAIDS) or aspirin [administered daily for more than one week at a scheduled dose intended for anti-inflammatory therapy]). All such drugs must have been discontinued ≥ 30 days prior to randomization.
  14. Any other concurrent medical or psychosocial condition likely to preclude compliance with the schedule of evaluations in the protocol or likely to confound the efficacy or safety observations of the study.
  15. Enrolled or planning to enroll in another clinical trial of an investigational agent while participating in this study.
  16. Any of the following laboratory values at Screening:

    • Hemoglobin (Hb) <11 mg/dL for men or <10 mg/dL for women.
    • Total white blood cell count (WBC) <2,500/mm3.
    • Absolute neutrophil count (ANC) <1,500/mm3.
    • Platelet count <75,000/mm3.
    • Serum albumin <3.2 g/dL.
    • Total bilirubin ≥2 mg/dL with direct bilirubin > 50% of total bilirubin.
    • Serum creatinine >1.0 x ULN.
    • Alpha-fetoprotein (AFP) >50 ng/mL (requires further evaluation, to rule-out hepatocellular carcinoma)
    • Creatinine clearance (CrCl) <0.83 mL/sec (<50 mL/min) calculated by the laboratory using the modified Cockcroft-Gault method.
    • Serum amylase or lipase ³1.5 x ULN.
    • Prothrombin time (PT) prolonged by >3 seconds or International Normalized Ratio (INR) > 1.5, based on the upper limits of normal (ULN) of the reference value, despite vitamin K administration.
  17. Use of any investigational drugs within 30 days or 5 half-lives of randomization, whichever is longer.
  18. Systemic malignancy within 5 years.
  19. Previous treatment with telbivudine.
  20. History of hypersensitivity to components of either telbivudine formulations, or to drugs with similar chemical structures.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00778596

Locations
Taiwan
Chang Gung Memorial Hospital
Linkou, Taoyuan County, Taiwan, 333
Chang Gung Memorial Hospital - Chiayi
Chiayi County, Taiwan
Chang Gung Memorial Hospital - Keelung
Keelung City, Taiwan
Chang Gung Memorial Hospital - Kaohsiung
Kaohsiung City, Taiwan
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Principal Investigator: Yun-Fan Liaw, MD Chang Gung Memorial Hospital
  More Information

No publications provided

Responsible Party: Chang Gung Memorial Hospital ( Yun-Fan Liaw/Visiting Staff )
Study ID Numbers: CST-L-1
Study First Received: October 21, 2008
Last Updated: November 12, 2008
ClinicalTrials.gov Identifier: NCT00778596     History of Changes
Health Authority: Taiwan: Institutional Review Board

Keywords provided by Chang Gung Memorial Hospital:
Hepatitis B
Telbivudine
Prednisolone

Study placed in the following topic categories:
Anti-Inflammatory Agents
Liver Diseases
Antineoplastic Agents, Hormonal
Hepatitis, Chronic
Methylprednisolone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hepatitis, Viral, Human
Methylprednisolone acetate
Prednisolone acetate
Neuroprotective Agents
Hormones
Glucocorticoids
Hepatitis
Virus Diseases
Digestive System Diseases
Hepatitis B, Chronic
Prednisolone
Hepatitis B
DNA Virus Infections
Peripheral Nervous System Agents
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Liver Diseases
Hepatitis, Chronic
Methylprednisolone
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hepatitis, Viral, Human
Antiemetics
Prednisolone acetate
Neuroprotective Agents
Hepadnaviridae Infections
Hormones
Hepatitis B, Chronic
Therapeutic Uses
Hepatitis B
Methylprednisolone Hemisuccinate
Antineoplastic Agents, Hormonal
Gastrointestinal Agents
Methylprednisolone acetate
Protective Agents
Glucocorticoids
Pharmacologic Actions
Virus Diseases
Hepatitis
Digestive System Diseases
Autonomic Agents
Prednisolone
DNA Virus Infections
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on May 07, 2009