Clinical Trial: Lactic Acidosis During Entecavir(ETV)Treatment

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: The Incidence of Lactic Acidosis During Entecavir Treatment in Chronic Hepatitis B Patients With Severe Cirrhosis or Hepatic Failure

Brief 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.

Detailed Summary:

Chronic hepatitis B virus (HBV) infection is the major cause of hepatic failure worldwide. Although the clinical course of HBV infection varies widely, the prognosis of decompensated liver cirrhosis is quite poor and the 5-year survival rate has been estimated to be only 14-35% without treatment. While the ultimate treatment of decompensated cirrhosis is orthotopic liver transplantation (OLT), several studies have suggested that anti-viral therapy can also improve the clinical outcomes in this group of patients.

Entecavir (ETV) is a potent cyclopentyl guanosine nucleoside inhibitor of the HBV polymerase. It has a higher anti-viral potency and a lower resistance rate compared to lamivudine (LAM), telbivudine or adefovir, when used for nucleoside/nucleotide-naïve patients. ETV has been shown to be effective in patients with both hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B, and compensated liver disease. As for patients with decompensated cirrhosis, the investigators recently reported that ETV can not only induce virological response but also improve underlying hepatic function, and thereby can reduce the need for OLT. The cumulative OLT-free survival at 1 year and 2 years was 87.1% and 83%, respectively with ETV treatment.

Despite this dramatic benefit from ETV treatment, a recent study reported that ETV may induce lactic acidosis in patients with severe hepatic and/or renal function impairment. Lange et al. reported that 5 of 16 patients with severely impaired liver function developed lactic acidosis during ETV treatment. Of note, all the five patients who developed lactic acidosis had MELD scores over 20, and no increased serum lactate concentrations were observed in other 11 patients whose MELD scores were below 18. The Child-Pugh score correlated insufficiently with a risk of
Sponsor: Asan Medical Center

Current Primary Outcome: Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L of Any Etiology [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 8 weeks ]

Original Primary Outcome: Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L of Any Etiology [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 8 weeks ]

Current Secondary Outcome:

• Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L Directly Related to NRTI [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks ]
  incidence of elevated venous lactate levels more than 2 mmol/L directly related to NRTI until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.
• Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L Caused by Etiologies Other Than NTRIs [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks ]
  incidence of elevated venous lactate levels more than 2 mmol/L caused by etiologies other than NTRIs until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.
• Frequency of Concomitant Prescribed Medications Possibly Associated With Lactic Acidosis Other Than NTRIs [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks ]
  Frequency of concomitant prescribed medications possibly associated with lactic acidosis other than NTRIs until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.
• Arterial pH and Anion Gap in Cases With Elevated Blood Lactate Levels (at the Time of Detection and Peak Levels [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks ]
  Arterial pH and anion gap in cases with elevated blood lactate levels (at the time of detection and peak levels until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.
• Overall OLT-free Survival [ Time Frame: Participants will be followed for the duration of hospital stay or outpatients visit, an expected average of 12 months ]
  Overall OLT-free survival until development of OLT and death and participants will be followed for the duration of hospital stay or outpatients visit, an expected average of 12 months

Original Secondary Outcome: Same as current

Information By: Asan Medical Center

Dates:
Date Received: May 11, 2011
Date Started: May 2011
Date Completion:
Last Updated: March 3, 2015
Last Verified: March 2015