NCT00135798

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
79

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2005

Typical duration for phase_2

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 26, 2005

Completed
6 days until next milestone

Study Start

First participant enrolled

September 1, 2005

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2009

Completed
3.3 years until next milestone

Results Posted

Study results publicly available

April 4, 2013

Completed
Last Updated

April 23, 2013

Status Verified

April 1, 2013

Enrollment Period

4.3 years

First QC Date

August 24, 2005

Results QC Date

June 13, 2012

Last Update Submit

April 11, 2013

Conditions

Hepatitis C

Keywords

Hepatitis CRibavirinPegInterferon alfa2b

Outcome Measures

Primary Outcomes (2)

  • Patients Who Are Negative for Hepatitis C Virus (HCV) RNA at 3 Months Post-transplant: Intent-to-Treat Analysis (ITT)

    Post-transplant virologic response (pTVR) defined as undetectable HCV RNA at week 12 after liver transplantation.

    3 months post-transplant

  • Patients Who Are Negative for HCV RNA at 3 Months Post-transplant: Per-Protocol Analysis (PP)

    Post-transplant virologic response (pTVR) defined as undetectable HCV RNA at week 12 after liver transplantation, analysed among patients who received treatment.

    3 months post-transplant

Secondary Outcomes (2)

  • Patients With Combined Virologic Response (CVR): Intent-to-Treat Analyses (ITT)

    Pre-transplant and 3 months post-transplant

  • Patients With Combined Virologic Response (CVR): Per-Protocol Analysis (PP)

    Pre-transplant and 3 months post-transplant

Study Arms (3)

LADR Treatment, Genotypes 1,4,6

EXPERIMENTAL

Subjects randomized to low accelerating dose regimen (LADR) treatment

Drug: LADR Treatment

Standard care

NO INTERVENTION

Subjects randomized to Standard Care group, Genotypes 1,4,6

LADR treatment, Genotypes 2,3

EXPERIMENTAL

Subjects randomized to low accelerating dose regimen (LADR) treatment.

Drug: LADR Treatment

Interventions

LADR TreatmentDRUG

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.

Also known as: PEG-Intron; Rebetol, Low Accelerated Dosing Regimen
LADR Treatment, Genotypes 1,4,6LADR treatment, Genotypes 2,3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

University of California Los Angeles

Los Angeles, California, 90095-7054, United States

Location

University of California San Francisco

San Francisco, California, 94143-0538, United States

Location

University of Colorado

Denver, Colorado, 80262, United States

Location

Northwestern University Division of Transplantation

Chicago, Illinois, 60611, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Related Publications (5)

  • 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. doi: 10.1002/hep.20793.

    PMID: 16025497BACKGROUND

  • 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. doi: 10.1002/lt.20189.

    PMID: 15237368BACKGROUND

  • Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger 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. doi: 10.1056/NEJMoa020047.

    PMID: 12324553BACKGROUND

  • 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. doi: 10.1016/s0140-6736(01)06102-5.

    PMID: 11583749BACKGROUND

  • 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.

    PMID: 22821361RESULT

MeSH Terms

Conditions

Hepatitis C

Interventions

peginterferon alfa-2bRibavirin

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Failure to reach target of 84 transplanted patients (47 achieved); Inability to complete planned 12 weeks of treatment for some; Incomplete HCV RNA follow up; Inconsistent limits of detection of HCV RNA; Noncompliance with assigned treatment.

Results Point of Contact

Title
Gregory T. Everson, M.D., Director of Hepatology
Organization
University Colorado, Denver
greg.everson@UCDenver.edu
720-848-2245

Study Officials

  • Gregory T. Everson, MD

    University of Colorado, Denver

    STUDY CHAIR

  • James Everhart, MD

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

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Division of Digestive Diseases and Nutrition

Study Record Dates

First Submitted

August 24, 2005

First Posted

August 26, 2005

Study Start

September 1, 2005

Primary Completion

December 1, 2009

Study Completion

December 1, 2009

Last Updated

April 23, 2013

Results First Posted

April 4, 2013

Record last verified: 2013-04

Locations

US(8)