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

Cirrhosis Clinical Trial

Official title:

Randomized, Double-Blind Trial of Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00076336
• Other study ID #: CLDT600A2301
• Status: Completed
• Phase: Phase 3
• First received: January 20, 2004
• Last updated: August 4, 2011
• Start date: December 2003

Study information

• Verified date: August 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cirrhosis
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Liver Cirrhosis

Intervention

Drug:
• Telbivudine
600mg/day oral tablet for 104 weeks
• Lamivudine
100mg/day oral tablet for 104 weeks
• Placebo
Telbivudine matching placebo or lamivudine matching placebo tablet.

Locations

Country	Name	City	State
India	Novartis	New Delhi
Latvia	Novartis	Riga
Malaysia	Novartis	Kuala Lumpur
Poland	Novartis	Krakow
Russian Federation	Novartis	Moscow
Turkey	Novartis	Istanbul
Vietnam	Novartis	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Australia,  Canada,  China,  France,  Germany,  India,  Israel,  Korea, Republic of,  Latvia,  Malaysia,  New Zealand,  Poland,  Russian Federation,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

References & Publications (1)

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 O

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinical Response	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.	From Baseline to Week 52	Yes
Secondary	Time to Initial Clinical Response	Time to Clinical Response defined as the number of days elapsed from the baseline visit to achieving initial Clinical Response.	From Baseline to Week 104	Yes
Secondary	Duration of Initial Clinical Response	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.	Baseline to Week 104	No
Secondary	Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 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.	From Baseline to weeks 52 and 104	Yes
Secondary	Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score	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).	Baseline and Week 104	Yes