Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Everolimus as Inhibitor of Fibrosis Progression in Liver Transplant Patients With Recurrence of Hepatitis C Viral Infection (REVERT)

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.
 
ClinicalTrials.gov Identifier: NCT00582738
Recruitment Status : Terminated
First Posted : December 28, 2007
Results First Posted : September 6, 2012
Last Update Posted : September 6, 2012
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE December 12, 2007
First Posted Date  ICMJE December 28, 2007
Results First Submitted Date  ICMJE January 10, 2012
Results First Posted Date  ICMJE September 6, 2012
Last Update Posted Date September 6, 2012
Study Start Date  ICMJE December 2007
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2012)
Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant. [ Time Frame: baseline, 24 Months ]
Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite Decrease in score from baseline indicates improvement
Original Primary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
Difference in fibrosis staging scores (measured by the Ishak-knodell staging score) between baseline and 24 months post randomization for each patient [ Time Frame: 2 yrs ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2012)
  • Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization [ Time Frame: Baseline, 12 months, 24 months ]
    Metavir Score: F0=No fibrosis; F1=Portal fibrosis without septa; F2=Portal fibrosis with rare septa; F3=Numerous septa without cirrhosis Decrease in score from baseline indicates improvement
  • Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups [ Time Frame: 24 Months ]
  • Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months [ Time Frame: 12 months, 24 months ]
  • Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups [ Time Frame: 12 months, 24 months/EOS ]
    GFR Month 9 value if available, otherwise minimal first year post-randomization available value. Imputation rule of missing Month 24 GFR values: GFR Month 18 value if available, otherwise Month 12 GFR is used. Least square means are from an ANCOVA model containing treatment as factor and baseline eGFR as a covariate.
  • Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) [ Time Frame: baseline, 12 months, 24 months ]
    Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite
  • Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry [ Time Frame: baseline, 12 and 24 months ]
    The Fibrosure test is the combination of Fibro-test + Acti-test. FibroTest (FT) was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase (GGT). FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and >= 0.59 is cirrhosis. Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase (ALT). ActiTest (AT) was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and >= 0.61 indicates severe necrosis If 12-month Actitest value was the last available assessment, the value is used to impute the final staging score(End of Study)
  • Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis [ Time Frame: baseline to month 24 ]
    Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite.
  • Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization [ Time Frame: baseline, 12 months, 24 months/EOS ]
    End of Study (EOS) endpoint is the last available assessment on or after Month 12. A reduction of at least two logs in HCV RNA viral load was considered as success
Original Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
Mean fibrosis staging scores measured by the Ishak-knodell staging score and Metavir staging score at 12/24 months and mean change at 12 post randomization Inflammatory Acti-test and fibrosis Fibro-testcomponents of Fibrosure TM and on fibrosi [ Time Frame: 2 yrs ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Everolimus as Inhibitor of Fibrosis Progression in Liver Transplant Patients With Recurrence of Hepatitis C Viral Infection
Official Title  ICMJE A Randomized, Controlled, Open Label, Two Arms, Exploratory Study to Evaluate the Effect of Everolimus on Histologically Assessed Fibrosis Progression (Ishak-Knodell) in Liver Transplant Recipients With Recurrent Hepatitis C Viral Infection as Compared to Standard Treatment.
Brief Summary This study will assess the efficacy of everolimus as an inhibitor of fibrosis progression in liver transplant patients who have a recurrence of hepatitis C viral infection in the transplant
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Hepatitis C
Intervention  ICMJE
  • Drug: CsA-TAC (standard Treatment)
    Continuation of current immunosuppressive regimen (continuation of CNI with or without MPA, with or without steroids) / no everolimus introduction.
  • Drug: Everolimus
    Hepatitis C recurrence after orthotopic liver transplantation (OLT)
Study Arms  ICMJE
  • Active Comparator: CsA-TAC
    Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
    Intervention: Drug: CsA-TAC (standard Treatment)
  • Experimental: everolimus
    Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
    Intervention: Drug: Everolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 2, 2012)
43
Original Estimated Enrollment  ICMJE
 (submitted: December 21, 2007)
50
Actual Study Completion Date  ICMJE January 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients 18 - 65 years of age
  • Recipients of deceased or living donors
  • Patients who had undergone primary liver transplantation at least 6 months before enrolment
  • Recurrent Hepatitis C viral infection and histologically confirmed liver fibrosis (stage I-IV in the Ishak-Knodell scale) obtained at baseline or within the previous 6 months to the date of enrolment
  • Patients receiving tacrolimus or cyclosporine micro-emulsion with or without - Mycophenolic acid (MPA), with or without steroids.
  • Absence of acute rejection episodes within the previous 6 months to the date of enrolment
  • Patient in whom an allograft biopsy will not be contraindicated
  • Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 24 months
  • Patients with Hepatocellular carcinoma (HCC) within the University California, San Francisco (UCSF) Criteria and no recurrence for at least 18 months after OLT.

Exclusion Criteria:

  • Recipients of multiple organ transplants or patients who have undergone retransplantation
  • Current biliary complications
  • History of drug or alcohol abuse within 1 year before enrolment
  • Patients treated with anti-hepatitis C virus treatment at the time of enrollment or within the previous month to the date of enrolment
  • Co-infection with Hepatitis B virus (HBV) or Human Immunodeficiency Virus (HIV)
  • Patients with Leukocyte count (WBC) < 3000/mm3, platelet count < 75000/mm3 or Hemoglobin (Hb) < 8 g/dl
  • Patients with proteinuria >1g/24 hours
  • Patient with a current severe systemic infection

Other protocol defined inclusion/exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00582738
Other Study ID Numbers  ICMJE CRAD001H2301
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP