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: August 12, 2014
Last verified: August 2014
  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
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 ] [ 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)


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 ] [ 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


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 and standard antiviral treatment Drug: cyclosporin (Neoral)
Neoral capsules bid, dose adjusted according to blood concentrations given for entire duration of study (80 weeks).
Active Comparator: tacrolimus + standard antiviral treatment Drug: tacrolimus
Tacrolimus capsules bid, dosed according to blood concentrations, given for entire duration of study(80 weeks).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Liver transplantation performed at least 6 months and up to 10 years prior randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular carcinoma (HCC) within Milan or UCSF criteria
  • Immunosuppressive regimen based on tacrolimus - (twice or once daily) for at least 6 months prior randomization
  • Diagnosis of HCV genotypes 1 or 4 infection confirmed 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 (> 1.7 mg/dL) or eGFR < 50 ml/min ([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 direct bilirubin >2 ULN, 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 neutrophils < 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

  Hide Study Locations
Locations
United States, Arizona
Novartis Investigative Site
Phoenix, Arizona, United States, 85054
United States, California
Novartis Investigative Site
Palo Alto, California, United States, 95128
Novartis Investigative Site
San Francisco, California, United States, 94143-2205
United States, Florida
Novartis Investigative Site
Gainesville, Florida, United States, 32610
United States, North Carolina
Novartis Investigative Site
Chapel Hill, North Carolina, United States, 27599-7211
United States, Oklahoma
Novartis Investigative Site
Oklahoma City, Oklahoma, United States, 73112
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030-2400
Novartis Investigative Site
Houston, Texas, United States, 77030
United States, Wisconsin
Novartis Investigative Site
Madison, Wisconsin, United States, 53792
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1070
Brazil
Novartis Investigative Site
Fortaleza, CE, Brazil, 60430-270
Novartis Investigative Site
São Paulo, SP, Brazil, 04023-900
Canada, Alberta
Novartis Investigative Site
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
Novartis Investigative Site
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Manitoba
Novartis Investigative Site
Winnipeg, Manitoba, Canada, R3E 0W3
Canada, Ontario
Novartis Investigative Site
London, Ontario, Canada, N6A 4G5
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2C4
Colombia
Novartis Investigative Site
Bogotá, Cundinamarca, Colombia, 110111
Novartis Investigative Site
Bogotá, Colombia
France
Novartis Investigative Site
Creteil, France, 94000
Novartis Investigative Site
Lyon Cedex 04, France, 69317
Novartis Investigative Site
Montpellier, France, 34295
Novartis Investigative Site
Paris, France, 75012
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Novartis Investigative Site
Villejuif, France, 94800
Germany
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Muenchen, Germany, 81377
Italy
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Padova, PD, Italy, 35128
Novartis Investigative Site
Udine, UD, Italy, 33100
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 120-752
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 135-710
Novartis Investigative Site
Seoul, Korea, Republic of, 137-701
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 123182
Novartis Investigative Site
Moscow, Russian Federation, 129010
Spain
Novartis Investigative Site
Oviedo, Asturias, Spain, 33006
Novartis Investigative Site
Valladolid, Castilla y Leon, Spain, 47012
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Barcelona, Cataluña, Spain, 08035
Novartis Investigative Site
Santiago de Compostela, Galicia, Spain, 15706
Switzerland
Novartis Investigative Site
Zurich, Switzerland, 8091
United Kingdom
Novartis Investigative Site
Birmingham, United Kingdom, B15 2TT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( 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: August 12, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
France: Ministry of Health
Germany: Ministry of Health
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Korea: Food and Drug Administration
Romania: Ministry of Public Health
Russia: Ministry of Health of the Russian Federation
Spain: Ministry of Health
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Tacrolimus
Antiviral Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014