Adefovir and Lamivudine for Entecavir Resistance (ALTER Study)

• Status: Completed
• Trial end date: 2014-02-01
• Target enrollment: 0
• Participant gender: All

Summary

• Entecavir has been one of the option for treatment of lamivudine resistant chronic hepatitis B (CHB).

• In case of entecavir resistance, adefovir could be used. However, sequential monotherapy may result in multidrug resistance.

• It is thought that adefovir and lamivudine combination therapy reduce the risk of adefovir resistance, thereby continued therapy will lead to suppression of hepatitis B virus (HBV) DNA to be undetectable in patients with entecavir resistance.

• This study aim to evaluate the efficacy of adefovir and lamivudine combination therapy in CHB patients with entecavir resistance.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Korea University
• Collaborator: GlaxoSmithKline
• Treatments: Adefovir; Adefovir dipivoxil; Entecavir; Lamivudine

Criteria

Inclusion Criteria:

1. Chronic hepatitis B patients (positive HBsAg > 6 months)

2. Age > 18 year old

3. History of treatment with entecavir more than 6 months

4. Proven entecavir resistant mutation (rtT184S/A/I/L/G/C/M, rtS202G/C/I, or rtM250I/V)

5. HBV DNA level> 2000 IU/mL

6. Compensated liver disease (Child-Pugh-Turcotte score over 7; prothrombin time prolonged more than 3 sec above ULN or INR over 1.5; serum albumin >3 g/dL; total bilirubin <2.5 mg/dL; No history of variceal bleeding, ascites, or hepatic encephalopathy)

7. Patients willing to give informed consent

Exclusion Criteria:

1. Out of inclusion criteria

2. Any one of following

• Serum phosphorus level under 2.4 mg/dL

• Serum creatinine level over 1.5 mg/dL or creatinine clearance <50 mL/min

• Absolute neutrophil count lower than 1000 cell/mL

• Hb level under 10 g/dL (male), under 9 g/dL (female)

• Serum AFP >100 ng/mL

3. History of treatment with interferon-alfa, thymosin-alfa 1, or nucleos(t)ide analogue other than entecavir in 6 months of screening

4. History of adefovir resistance (detection of rtA181T/Vor rtN236T at screening or in the past)

5. Recipient of organ transplantation

6. Positive antibody test to HIV, HCV or HDV

7. Pregnant or breast feeding women

8. Patients with hepatocellular carcinoma or uncontrolled malignant disease

9. Habitual alcohol drinker (>140 g/week for men, >70 g/week for women) -