Lactic Acidosis During Entecavir(ETV)Treatment

• Status: Terminated
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to investigate whether entecavir treatment increases the incidence of lactic acidosis compared to another nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), lamivudine, and/or no NRTI treatment, in patients with cirrhosis or hepatic failure whose Model for End stage Liver Disease (MELD) scores are over 18.

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

Details

• Lead Sponsor: Asan Medical Center
• Treatments: Entecavir; Lamivudine

Criteria

1. for ETV or LAM group

Inclusion criteria:

• 18 and more than 18 years, and less than 65 years

• HBV-related liver cirrhosis or acute-on-chronic liver failure

• Prior documentation of chronic HBV infection at least 6 months before randomization

• MELD score 18 and more than 18

• Venous blood lactate level 2 and less than 2 mmol/L

Exclusion criteria:

• Age of 65 or older, or younger than 18

• Patients with acute hepatitis B including acute liver failure

• Acute-on-chronic liver failure precipitated by acute hepatitis A or acetaminophen intoxication

• MELD score less than 18

• entecavir, lamivudine, telbivudine, clevudine, adefovir or tenofovir treatment continued longer than 3 months before entry.

• Evidence of genotypic or virological resistance to lamivudine, clevudine, telbivudine, or adefovir

• Patients with elevated venous blood lactate levels more than 2 mmol/L

• Recent episodes of active infection, hypotension (systolic blood pressure less than 90 mmHg), gastrointestinal or other active bleeding within 2 weeks before entry

• Any alcohol intake within 2 weeks before entry

• Recent use of acetaminophen, epinephrine, metformin, iron, isoniazid, propofol, salicylate, sulfasalazine, or valproic acid within 2 weeks before entry. Use of lactulose is permitted.

• Presence of hepatocellular carcinoma. Patients with hepatocellular carcinoma meeting the Milan criteria can be permitted.

• Any cancer other than hepatocellular carcinoma except cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated at least 3 years prior to entry is permitted.

• Patients with HIV infection

• Female patients in pregnancy

2. for no NRTI group

Inclusion criteria:

• Age of 65 or older, or younger than 18

• Liver cirrhosis or acute-on-chronic liver failure not related with HBV

• MELD score 18 and more than 18

• Venous blood lactate level 2 and less than 2 mmol/L

Exclusion criteria:

• Age of 65 or older, or younger than 18

• Patients with positive HBsAg or IgM anti-HBc

• Acute-on-chronic liver failure precipitated by acute hepatitis A or acetaminophen intoxication

• MELD score less than 18

• Patients with elevated venous blood lactate levels more than 2 mmol/L

• Recent episodes of active infection, hypotension (systolic blood pressure less than 90 mmHg), gastrointestinal or other active bleeding within 2 weeks before entry

• Any alcohol intake within 2 weeks before entry

• Recent use of acetaminophen, epinephrine, metformin, iron, isoniazid, propofol, salicylate, sulfasalazine, or valproic acid within 2 weeks before entry. Use of lactulose is permitted.

• Presence of hepatocellular carcinoma. Patients with hepatocellular carcinoma within Milan criteria can be permitted.

• Any cancer other than hepatocellular carcinoma except cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated at least 3 years prior to entry is permitted.

• Patients with HIV infection

• Female patients in pregnancy