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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
  Purpose
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.

Condition Intervention Phase
Hepatitis C
Liver Transplantation
Drug: cyclosporin (Neoral)
Drug: tacrolimus (Prograf)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ]
    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)


Secondary Outcome Measures:
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Defined as number of patients with dose reduction or discontinuation of AV therapy due to poor tolerability


Enrollment: 92
Study Start Date: September 2009
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Active Comparator: tacrolimus
Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.
Drug: tacrolimus (Prograf)
Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00938860

  Show 45 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00938860     History of Changes
Other Study ID Numbers: COLO400A2430  2009-010806-12 
Study First Received: July 13, 2009
Results First Received: April 25, 2014
Last Updated: May 5, 2015

Keywords provided by Novartis:
Hepatitis C
liver transplantation
anti-viral therapy

Additional relevant MeSH terms:
Hepatitis C
Hepatitis
Hepatitis A
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Liver Diseases
Digestive System Diseases
Enterovirus Infections
Picornaviridae Infections
Tacrolimus
Cyclosporins
Cyclosporine
Benzocaine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on February 20, 2017