Pre-Transplant Treatment to Prevent Recurrence of Hepatitis C After Liver Transplantation (LADR)

This study has been completed.
Sponsor:
Collaborators:
Schering-Plough
Ortho Biotech Clinical Affairs, L.L.C.
Information provided by (Responsible Party):
Averell Sherker, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00135798
First received: August 24, 2005
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to learn if pre-liver transplant treatment, using peginterferon plus ribavirin, will clear hepatitis C virus (HCV) RNA from the blood in HCV-infected recipients and reduce the risk of recurrent HCV and allograft hepatitis following liver transplant.


Condition Intervention Phase
Hepatitis C
Drug: LADR Treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Adult-to-adult Living Donor Liver Transplantation Cohort Study (A2ALL) Low Accelerated Dosing Regimen (LADR) Protocol: Pre-Transplant Treatment to Prevent Recurrence of Hepatitis C Virus (HCV) After Liver Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Patients Who Are Negative for Hepatitis C Virus (HCV) RNA at 3 Months Post-transplant: Intent-to-Treat Analysis (ITT) [ Time Frame: 3 months post-transplant ] [ Designated as safety issue: No ]
    Post-transplant virologic response (pTVR) defined as undetectable HCV RNA at week 12 after liver transplantation.

  • Patients Who Are Negative for HCV RNA at 3 Months Post-transplant: Per-Protocol Analysis (PP) [ Time Frame: 3 months post-transplant ] [ Designated as safety issue: No ]
    Post-transplant virologic response (pTVR) defined as undetectable HCV RNA at week 12 after liver transplantation, analysed among patients who received treatment.


Secondary Outcome Measures:
  • Patients With Combined Virologic Response (CVR): Intent-to-Treat Analyses (ITT) [ Time Frame: Pre-transplant and 3 months post-transplant ] [ Designated as safety issue: No ]
    Intent-to-Treat (ITT) analyses of all patients. Combined Virologic Response (CVR), which includes both sustained virologic response pre-transplant (SVR) and post-transplant virologic response (pTVR)

  • Patients With Combined Virologic Response (CVR): Per-Protocol Analysis (PP) [ Time Frame: Pre-transplant and 3 months post-transplant ] [ Designated as safety issue: No ]
    Per-Protocol (PP) analyses of all patients. Combined Virologic Response (CVR)includes both sustained virologic response pre-transplant (SVR) and post-transplant virologic response (pTVR), analysed among patients who received treatment.


Enrollment: 79
Study Start Date: September 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LADR Treatment, Genotypes 1,4,6
Subjects randomized to low accelerating dose regimen (LADR) treatment
Drug: LADR Treatment

PEG-Intron (peginterferon alfa-2b (PEGIFN)) Redipen; Rebetol (ribavirin (RBV) United States Pharmacopeia (USP)) Capsules:

Treatment was initiated with PEGIFN 0.75 µg/kg/week and RBV 600 mg/day. Dose escalations were performed at weeks 1 (PEGIFN 1.5 µg/kg/week and RBV 800 mg/day), 2 (RBV 1.0 g/day), and 3 (RBV 1.2 g/day for patients who weighed more then 75 kg) based upon patient tolerance and weekly blood counts. Once a patient reached the target RBV dose of 1-1.2 g/day (approximately 10.6 to 13.2 mg/kg/day), no further increases in RBV dose were made. Subsequent doses of PEGIFN and RBV were adjusted based upon adverse events, patient tolerability, and blood counts. If the highest tolerated dose of PEGIFN was <0.5 ug/kg, PEGIFN was permanently discontinued.

Other Names:
  • PEG-Intron; Rebetol
  • Low Accelerated Dosing Regimen
No Intervention: Standard care
Subjects randomized to Standard Care group, Genotypes 1,4,6
Experimental: LADR treatment, Genotypes 2,3
Subjects randomized to low accelerating dose regimen (LADR) treatment.
Drug: LADR Treatment

PEG-Intron (peginterferon alfa-2b (PEGIFN)) Redipen; Rebetol (ribavirin (RBV) United States Pharmacopeia (USP)) Capsules:

Treatment was initiated with PEGIFN 0.75 µg/kg/week and RBV 600 mg/day. Dose escalations were performed at weeks 1 (PEGIFN 1.5 µg/kg/week and RBV 800 mg/day), 2 (RBV 1.0 g/day), and 3 (RBV 1.2 g/day for patients who weighed more then 75 kg) based upon patient tolerance and weekly blood counts. Once a patient reached the target RBV dose of 1-1.2 g/day (approximately 10.6 to 13.2 mg/kg/day), no further increases in RBV dose were made. Subsequent doses of PEGIFN and RBV were adjusted based upon adverse events, patient tolerability, and blood counts. If the highest tolerated dose of PEGIFN was <0.5 ug/kg, PEGIFN was permanently discontinued.

Other Names:
  • PEG-Intron; Rebetol
  • Low Accelerated Dosing Regimen

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult (18 or older)
  • LDLT candidate
  • HCV RNA positive
  • Expected time on treatment is at least 12 weeks
  • Candidates for DDLT who are listed for transplantation and meet UNOS criteria for MELD upgrade for HCC

Exclusion Criteria:

  • Severe cytopenia (polymorphonuclear (PMN) leukocytes < 750, OR hemoglobin [Hgb] < 10 g/dL, OR platelet count < 35,000/mm3)
  • Uncontrolled depression or psychiatric disease characterized by current symptoms of major depression or other psychiatric disease or increase in medication for major depression or other psychiatric disease within the past three months.
  • Uncontrolled cardiopulmonary disease characterized by myocardial infarction, coronary artery bypass graft surgery, Percutaneous coronary intervention, or unstable angina within the past three months.
  • Uncontrolled autoimmune disease characterized by current symptoms of autoimmune disease or increase in medications within the last three months.
  • Autoimmune hepatitis
  • Active substance abuse within 6 months of initiation of treatment
  • Known intolerance or serious adverse event during prior therapy with interferon or ribavirin
  • Prior nonresponse after at least 24 weeks of full dose treatment with peginterferon plus ribavirin
  • Laboratory Model for End-Stage Liver Disease (MELD) score >20. Patients with laboratory MELD score 21-25 may be enrolled if deemed appropriate by the site investigator
  • Serum creatinine >2.2 mg/dL
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00135798

Locations
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095-7054
University of California San Francisco
San Francisco, California, United States, 94143-0538
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80262
United States, Illinois
Northwestern University Division of Transplantation
Chicago, Illinois, United States, 60611
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Virginia Commonwealth University
Richmond, Virginia, United States, 23219
Sponsors and Collaborators
Schering-Plough
Ortho Biotech Clinical Affairs, L.L.C.
Investigators
Study Chair: Gregory T. Everson, MD University of Colorado, Denver
Study Director: James Everhart, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Publications:

Responsible Party: Averell Sherker, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00135798     History of Changes
Other Study ID Numbers: A2ALL LADR Protocol 62498(IND), U01DK062498, U01DK062536, U01DK062444, U01DK062467, U01DK062483, U01DK062484, U01DK062494, U01DK062496, U01DK062505, U01DK062531, CRADA through NIH-NIDDK, CTA through NIH-NIDDK, HRSA, ASTS
Study First Received: August 24, 2005
Results First Received: June 13, 2012
Last Updated: April 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Hepatitis C
Ribavirin
PegInterferon alfa2b

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Recurrence
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Disease Attributes
Pathologic Processes
Peginterferon alfa-2b
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014