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Lactic Acidosis During Entecavir(ETV)Treatment (ETV)

This study has been terminated.
(Tenofovir has become available in Korea.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01354652
First Posted: May 17, 2011
Last Update Posted: March 23, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Han Chu Lee, Asan Medical Center
  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
Intervention Model: Parallel Assignment
Masking: None (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:


Further study details as provided by Han Chu Lee, 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 ]
    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 ]
    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


Enrollment: 5
Study Start Date: May 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: entecavir

Oral 0.5mg/day until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18.

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

Oral 100mg/day lamivudine until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18.

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
hepatitis C virus associated LC patients for the calculation of lactic acidosis incidence

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01354652


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

Responsible Party: Han Chu Lee, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01354652     History of Changes
Other Study ID Numbers: Hanchu3915
First Submitted: May 11, 2011
First Posted: May 17, 2011
Results First Submitted: January 18, 2015
Results First Posted: February 20, 2015
Last Update Posted: March 23, 2015
Last Verified: March 2015

Keywords provided by Han Chu Lee, 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
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents