Pre-Transplant Treatment to Prevent Recurrence of Hepatitis C After Liver Transplantation (LADR)
This study has been completed.
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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
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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:
|
|
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:
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| 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
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00135798
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
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
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 C Hepatitis Hepatitis A Recurrence Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Liver Diseases Digestive System Diseases |
Enterovirus Infections Picornaviridae Infections Disease Attributes Pathologic Processes Peginterferon alfa-2b Ribavirin Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on September 26, 2016