Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

• ClinicalTrials.gov Identifier: NCT00076336
• Recruitment Status: Completed
• First Posted: January 22, 2004
• Results First Posted: September 5, 2011
• Last Update Posted: September 5, 2011
• Sponsor: Novartis Pharmaceuticals
• Information provided by: Novartis

Study Description

Brief Summary:

This research study was conducted to compare the safety and effectiveness of the investigational medication, LdT (Telbivudine) versus Lamivudine, a drug currently approved by the US, European and Asian Health Authorities for the treatment of Hepatitis B infection. The results for patients taking LdT will be compared to results for patients taking lamivudine.

Condition or disease	Intervention/treatment	Phase
Hepatitis; Hepatitis B, Chronic; Cirrhosis	Drug: Telbivudine; Drug: Lamivudine; Drug: Placebo	Phase 3

Detailed Description:

Multicenter, multinational, randomized, double-blind study designed to compare the safety and efficacy of telbivudine (600 mg/day) versus lamivudine (100 mg/day) for 104 weeks in adults with decompensated chronic hepatitis B and evidence of cirrhosis. Patients were pre-stratified by screening Child-Turcotte-Pugh score (CTP score < 9 or ≥ 9) and ALT level (within normal limits (WNL) or > 1.0 x ULN) to help assure similar degrees of hepatic insufficiency and liver inflammation on both treatment arms. After 104 weeks of treatment, participants were followed-up with for an additional 16 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind Trial of Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis
• Study Start Date: December 2003
• Actual Primary Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Telbivudine 600 mg; Participants received Telbivudine 600 mg and a matching lamivudine placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment.	Drug: Telbivudine; 600mg/day oral tablet for 104 weeks; Other Name: LDT600; Drug: Placebo; Telbivudine matching placebo or lamivudine matching placebo tablet.
Active Comparator: Lamivudine 100 mg; Lamivudine 100 mg and a Telbivudine matching placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment.	Drug: Lamivudine; 100mg/day oral tablet for 104 weeks; Drug: Placebo; Telbivudine matching placebo or lamivudine matching placebo tablet.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Clinical Response [ Time Frame: From Baseline to Week 52 ]
   Clinical response defined as achieving all of the following 3 criteria on at least 2 consecutive visits or at the last on-treatment visit: Serum hepatitis B virus (HBV) DNA < 4 log10 copies/mL, normal Alanine transaminase (ALT) level (ALT ≤ Upper Limit of Normal (ULN)), and improvement (a 2- point or greater reduction in Child-Turcotte-Pugh (CTP) score) or stabilization (not more than a 1-point change in CTP score), compared to the baseline value. CTP scores range from 5-15, higher scores indicate more liver impairment. For Improvement/Stabilization, either of the individual criteria were met.

Secondary Outcome Measures :

1. Time to Initial Clinical Response [ Time Frame: From Baseline to Week 104 ]
   Time to Clinical Response defined as the number of days elapsed from the baseline visit to achieving initial Clinical Response.
2. Duration of Initial Clinical Response [ Time Frame: Baseline to Week 104 ]
   Kaplan-Meier method was used. The duration was calculated as: date of last visit before initial loss of clinical response - date of initial clinical response occurred+1. If a patient did not lose clinical response, it was then censored at the efficacy overall censoring date.
3. Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 [ Time Frame: From Baseline to weeks 52 and 104 ]
   Child-Turcotte-Pugh (CTP) uses 2 clinical variables, ascites and encephalopathy, and 3 laboratory parameters, serum bilirubin, albumin, and prothrombin time. Each variable is assigned a score from 1 to 3, with the combined score comprising the CTP score range of 5 to 15 points. Higher scores indicate more impaired liver function. "Worsening" of CTP score was defined as a 2-point or greater increase from baseline, "improvement" in CTP score was defined as a 2-point or greater reduction from baseline, and "stabilization" of CTP score was defined as a change of 1-point or less from baseline.
4. Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score [ Time Frame: Baseline and Week 104 ]
   Modified CTP was calculated using the 3 biochemical-components (serum bilirubin, albumin, and prothrombin). Total scores range from 3-9; higher scores indicate more liver impairment. Improvement was defined as 2-point or greater reduction in score from baseline. Stabilization comprises a score change of 1-point or less from baseline. Worsening of CTP score was defined as a 2-point or greater increase from baseline. The rationale for assessing changes in this modified (3-component) CTP score is that this maneuver removed the two subjective components of CTP scoring (ascites and encephalopathy).

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Documented decompensated chronic hepatitis B defined by all of the following: 1. Clinical history compatible with decompensated chronic hepatitis B related cirrhosis; 2. Child-Turcotte-Pugh score > 7 points.
• Evidence of hepatic cirrhosis or portal hypertension.

Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

• Patient is pregnant or breastfeeding.
• Patient is coinfected with hepatitis C virus (HCV), hepatitis D virus (HDV), or Human immunodeficiency virus (HIV).
• Patient previously received lamivudine, adefovir, or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog at any time
• Patient has received interferon or other immunomodulatory treatment for HBV infection in the 12 months before Screening for this study.

Other protocol-defined exclusion criteria may apply.

Contacts and Locations

  Show 28 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

Publications of Results:

E.J. Gane, H.L. Chan, G. Choudhuri, D.J. Suh4, A. Chutaputti, R. Safadi, T. Tanwandee, S. Thongsawat, N. Assy, S.K. Sarin, W. Bao, A. Trylesinski, C. Avila. TREATMENT OF DECOMPENSATED HBV-CIRRHOSIS: RESULTS FROM 2-YEARS RANDOMIZED TRIAL WITH TELBIVUDINE OR LAMIVUDINE. Journal of Hepatology 52, Supplement 1, Page S4. April 2010

• Responsible Party: External Affairs, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00076336 History of Changes
• Other Study ID Numbers: CLDT600A2301
• First Posted: January 22, 2004
• Results First Posted: September 5, 2011
• Last Update Posted: September 5, 2011
• Last Verified: August 2011

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Liver Cirrhosis; Fibrosis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Pathologic Processes; Lamivudine; Telbivudine; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents