Trial record 1 of 1 for:    NCT00938860
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Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C (SUSTAIN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00938860
First received: July 13, 2009
Last updated: May 5, 2015
Last verified: May 2015

July 13, 2009
May 5, 2015
September 2009
May 2013   (final data collection date for primary outcome measure)
Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
The achievement of SVR, defined as HCV RNA below limit of detection at the end of AV treatment, 24 weeks after end of AV treatment (W24 post). A dichotomous variable (SVR achieved: Yes/No) was computed. A patient was classified as non-responder (SVR not achieved) if HCV RNA was detectable at the completion of antiviral treatment, at W24post, or at any time between W24 and completion of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Sustained Virological Response as measured by HCV RNA by PCR [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00938860 on ClinicalTrials.gov Archive Site
  • Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Efficacy failure (biopsy proven acute rejection (BPAR), graft loss, or death
  • Number of Participants With Fibrosis Progression (Increase in Ishak-Knodell (IK) Score by at Least One Point From the Baseline) [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    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, Participants showing an increase of Ishak Knodell fibrosis score by at least one level (increase of ≥1)
  • Number of Participants of Rapid Viral Response (RVR) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    RVR defined as non-detectable HCV RNA 4 weeks after initiation of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
  • Number of Participants of Early Viral Response (EVR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    EVR defined as non-detectable HCV RNA or a ≥2 logs reduction of HCV RNA at 12 weeks after initiation of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
  • Number of Participants for the End of Treatment Response (ETR) [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    ETR defined as non-detectable HCV RNA at the completion of AV treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
  • Number of Participants of True Non-responder Rate [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Defined as failure to achieve at least a 2 log reduction of Hepatitis C virus (HCV) RNA. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
  • Number of Participants for Relapse Rate [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Defined as reappearance of detectable Hepatitis C Virus (HCV) RNA at 24 weeks after completion of antiviral treatment when HCV RNA was undetectable at the end of treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
  • Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Defined as number of patients with dose reduction or discontinuation of AV therapy due to poor tolerability
  • Compare rates of the composite endpoint of biopsy proven rejections (BPAR) death or graft loss [ Time Frame: Week 80 (EOS) ] [ Designated as safety issue: No ]
  • Assess the rate of fibrosis progression (Ishak-Knodell score) [ Time Frame: Week 80 (Eos) ] [ Designated as safety issue: No ]
  • Compare rates of Rapid Viral Response [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Compare rates of Early Viral Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Compare the End of Treatment Response [ Time Frame: Week 80 (EoS) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C
A Multi-center, Randomized, Open Label, Controlled Study to Compare the Sustained Virological Response During Treatment With Neoral or Tacrolimus in Maintenance Liver Transplant Recipients Treated With Pegylated Interferon and Ribavirin for Recurrent Hepatitis C

This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C
  • Liver Transplantation
  • Drug: cyclosporin (Neoral)
    Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
  • Drug: tacrolimus (Prograf)
    Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.
  • Experimental: Neoral
    Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
    Intervention: Drug: cyclosporin (Neoral)
  • Active Comparator: tacrolimus
    Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.
    Intervention: Drug: tacrolimus (Prograf)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
92
May 2013
May 2013   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Liver transplantation performed at least 6 months and up to 5 years prior randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular carcinoma (HCC) within Milan or UCSF criteria
  • Immunosuppresive regimen based on tacrolimus b.i.d.- (twice or once daily) for at least 6 months prior randomization
  • Diagnosis of HCV genotypes 1 or 4 infection prior to transplantationconfirmed at screening
  • Indication of treatment with Peg-IFN and ribavirin due to histological evidence of chronic HCV infection defined as a fibrosis stage equal or greater than 1 using the Ishak-Knodell scoring system (IK ≥1) in a liver biopsy performed at screening or up to 4 months prior to randomization.

Exclusion criteria:

  • Serum creatinine >150 μmol/L (1.6 7 mg/dL) or eGFR < 50 ml/min (4-variable Modification of Diet in Renal Disease [MDRD Cockcroft-Gault formula])
  • Multi-organ transplant recipients
  • Recent episode of steroid-treated acute rejection (AR) within 3 months prior to randomization, or >1 episode of steroid-treated AR in the last 6 months, or any number of steroid-resistant AR episodes in the last 6 months including evidence of chronic rejection or ductopenia
  • Evidence of conditions that could cause graft dysfunction other than HCV infection
  • Patients with signs of decompensated liver disease, defined as presence of ascites, variceal bleeding, encephalopathy or deteriorated hepatic synthetic function (albumin <3.5g/dL or, total direct bilirubin >1.5mg/dL or, INR >1.5)
  • Co-infection with HIV or Hepatitis B (defined as HBsAg-positive) at screening
  • Use of mTOR inhibitors (everolimus or sirolimus) in the 6 months prior to screening
  • Antiviral treatment for HCV administered at any time after liver transplantation
  • Patients on daily doses of corticosteroids higher than 5 mg/day
  • Patients with fibrosing cholestatic hepatitis
  • Patients with current diagnosis of malignancies, including lymphoproliferative disorders
  • Patients with platelet count <70,000/mm3 or neutrophiles <1,500/mm3
  • History of HCC outside Milan criteria based on radiology or UCSF criteria based on analysis of the explant
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Brazil,   Canada,   Colombia,   France,   Germany,   Italy,   Korea, Republic of,   Russian Federation,   Spain,   Switzerland,   United Kingdom
 
NCT00938860
COLO400A2430, 2009-010806-12
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2015

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