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Lactic Acidosis During Entecavir(ETV)Treatment

This study is not yet open for participant recruitment.
Verified May 2011 by Asan Medical Center
Sponsor:
Information provided by:
Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01354652
First received: May 11, 2011
Last updated: May 17, 2011
Last verified: May 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Lactic Acidosis
 Drug: entecavir, lamivudine
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Incidence of Lactic Acidosis During Entecavir Treatment in Chronic Hepatitis B Patients With Severe Cirrhosis or Hepatic Failure

Resource links provided by NLM:

MedlinePlus related topics: Cirrhosis
U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    incidence of elevated venous lactate levels more than 2 mmol/L of any etiology until development of lactic acidosis, orthotropic liver transplantation (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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 90
Study Start Date: May 2011
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: entecavir group
They will receive 0.5mg/day entecavir P.O 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.
 Drug: entecavir, lamivudine

entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

lamivudine: 100mg/day p.o 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.

Other Names:
  • Entecavir:baraclude
  • Lamivudine: zeffix
Active Comparator: lamivudine group
They will receive 100mg/day lamivudine P.O 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.
 Drug: entecavir, lamivudine

entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

lamivudine: 100mg/day p.o 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.

Other Names:
  • Entecavir:baraclude
  • Lamivudine: zeffix
No Intervention: no NRTI group Drug: entecavir, lamivudine

entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

lamivudine: 100mg/day p.o 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.

Other Names:
  • Entecavir:baraclude
  • Lamivudine: zeffix

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01354652

Contacts
Contact: Han Chu Lee, M.D +82-02-3010-3915 hch@amc.seoul.kr

Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Han Chu Lee, M.D Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine
  More Information

No publications provided

Responsible Party: Han Chu Lee, Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
ClinicalTrials.gov Identifier: NCT01354652     History of Changes
Other Study ID Numbers: Hanchu3915
Study First Received: May 11, 2011
Last Updated: May 17, 2011
Health Authority: Korea: Institutional Review Board

Keywords provided by Asan Medical Center:
lactic acidosis
entecavir
lamivudine

Additional relevant MeSH terms:
Acidosis
Acidosis, Lactic
Acid-Base Imbalance
Metabolic Diseases
Lamivudine
Entecavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 22, 2013