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

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ClinicalTrials.gov Identifier: NCT00135798

Recruitment Status : Completed

First Posted : August 26, 2005

Results First Posted : April 4, 2013

Last Update Posted : April 23, 2013

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)

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Hepatitis C	Drug: LADR Treatment	Phase 2

Show Detailed Description

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	79 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Study Start Date :	September 2005
Actual Primary Completion Date :	December 2009
Actual Study Completion Date :	December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C Liver Transplantation

Drug Information available for: Ribavirin Peginterferon Alfa-2b

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

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 ]
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 ]
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 ]
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 ]
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.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

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): 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

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

Additional Information:

Adult-to-Adult Living Donor Transplantation Cohort Study Website This link exits the ClinicalTrials.gov site

Publications of Results:

Everson GT, Terrault NA, Lok AS, Rodrigo del R, Brown RS Jr, Saab S, Shiffman ML, Al-Osaimi AM, Kulik LM, Gillespie BW, Everhart JE; Adult-to-Adult Living Donor Liver Transplantation Cohort Study. A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology. 2013 May;57(5):1752-62. doi: 10.1002/hep.25976. Epub 2013 Jan 17.

Other Publications:

Everson GT, Trotter J, Forman L, Kugelmas M, Halprin A, Fey B, Ray C. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology. 2005 Aug;42(2):255-62.

Stravitz RT, Shiffman ML, Sanyal AJ, Luketic VA, Sterling RK, Heuman DM, Ashworth A, Mills AS, Contos M, Cotterell AH, Maluf D, Posner MP, Fisher RA. Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation. Liver Transpl. 2004 Jul;10(7):850-8.

Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.


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 ( U.S. NIH Grant/Contract ) U01DK062536 ( U.S. NIH Grant/Contract ) U01DK062444 ( U.S. NIH Grant/Contract ) U01DK062467 ( U.S. NIH Grant/Contract ) U01DK062483 ( U.S. NIH Grant/Contract ) U01DK062484 ( U.S. NIH Grant/Contract ) U01DK062494 ( U.S. NIH Grant/Contract ) U01DK062496 ( U.S. NIH Grant/Contract ) U01DK062505 ( U.S. NIH Grant/Contract ) U01DK062531 ( U.S. NIH Grant/Contract ) CRADA through NIH-NIDDK ( Other Identifier: Schering-Plough ) CTA through NIH-NIDDK ( Other Identifier: Ortho-Biotech ) HRSA ( Other Identifier: Health Resources and Services Administration ) ASTS ( Other Identifier: American Society of Transplant Surgeons )
First Posted:	August 26, 2005 Key Record Dates
Results First Posted:	April 4, 2013
Last Update Posted:	April 23, 2013
Last Verified:	April 2013

Keywords provided by Averell Sherker, 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 Ribavirin Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action

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