Effect of Switching to Certican® in Viremia of Hepatitis C Virus in Adult Renal Allograft Recipients (CONCERVIC)
|Renal Allograft Hepatitis C||Drug: Everolimus Drug: Cyclosporine Drug: Tacrolimus||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
|Official Title:||A Prospective, Single-center, Open-label, Pilot Study to Investigate the Effect of Switching to Certican® in Viremia of Hepatitis C Virus in Adult Renal Allograft Recipients.|
- Change from baseline in viral load of hepatitis C virus at 12 months after randomization. [ Time Frame: Baseline,Months 3, 6, 9 and 12 after randomization ]HCV viremia will be measured by polymerase chain reaction (PCR)
- Incidence of acute allograft rejection [ Time Frame: Weeks 1, 2, 3, months 1, 3, 6, 9 and 12 after randomization ]All patients will perform at least 07 protocol visits and should be performed renal biopsy during screening phase and during the follow up if present renal dysfunction or proteinuria.
- Incidence of significant infections [ Time Frame: Weeks1, 2, 3 and months 1, 3, 6,9 and 12 after randomization ]During the study visits the patient will be evaluated by a doctor and it will perform blood tests to assess their clinical conditions.
- Development of proteinuria [ Time Frame: Months 1, 3, 6, 9 and 12 after randomization ]Spot urine sample for protein and creatinine will be performed.
- Development of malignance [ Time Frame: Weeks 1, 2, 3 and months 1, 3, 6, 9 and 12 after randomization ]Medical evaluation will be performed during the protocol visits and if necessary biopsy and exams of imaging to confirm any suspected.
- Development of dyslipidemia [ Time Frame: Months 1, 3, 6, 9 and 12 after randomization ]Lipid levels: total cholesterol, HLD, LDL and triglycerides will be performed.
- Development of liver impairment [ Time Frame: Months 1, 3, 6, 9, and 12 after randomization ]Blood chemistry: TGO/AST, TGP/ALT , GGT and alkaline phosphatase will be performed.
- Development of post-transplant diabetes [ Time Frame: Months 1, 3, 6, 9 and 12 ]Blood chemistry: Glucose will be performed.
- Development of hypertension [ Time Frame: Weeks 1, 2, 3 and months 1, 3, 6, 9 and 12 after randomization ]Vital signs will be performed
- Graft loss survival [ Time Frame: Weeks 1, 2 , 3 and months 1, 3 ,6, 9 and 12 after randomization ]Graft survival will be evaluated by our team doctor.
- Patient survival [ Time Frame: Weeks 1, 2, 3 and months 1, 3, 6, 9 and 12 after randomization ]Subject survival will be evaluated by our team doctor
|Study Start Date:||November 2011|
|Study Completion Date:||April 2015|
|Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
The conversion will be performed abruptly for all patients. Calcineurin inhibitor will be discontinued one day before the day of conversion (Day 1). Everolimus will be introduced on day 1 at dose of 3 mg/d (1,5mg bid), and then everolimus trough levels will be adjusted to achieve 6-10 ng/ml.
Active Comparator: Tacrolimus or Cyclosporine
Arm2(maintained):Tacrolimus or Cyclosporine+mycophenolate+prednisone
Trough level should be between 100 and 200ng/ml.Drug: Tacrolimus
Trough level should be between 5 and 10ng/ml.
The infection by hepatitis C virus (HCV) is the leading cause of chronic liver disease in renal transplant recipients.
The prevalence of pretransplantation anti-HCV is 11% to 49%. The impact of HCV infection on patient survival after renal transplant remains controversial. Some studies also showed that patients undergoing renal transplantation anti-HCV positive are associated with a reduction in graft and patient survival.Chronic infection of HCV is associated with an increased number of infections.
In HCV positive renal transplant patients have been shown that there is an increase from four to seven times in HCV viremia after transplantation compared to pretransplant.
To prevent viral replication, immunosuppression must be adapted, involving a balance between control of viral replication and rejection.
Biochemically, the NS5A protein has been linked to increased replication of the hepatitis C virus through p70S6K phosphopeptides. Sirolimus as inhibitor of pathway mTOR/p70S6K reduced in vivo phosphorylation of NS5A phosphopeptides and thus viral replication. Moreover, the mTOR protein has been proven in vitron to have a protective role against apoptosis in HCV infected cells (WAGNER et al., 2010).
Wagner et al. (2010) showed a beneficial effect of sirolimus on viral recurrence monitored by transaminases and viral load as well as by histological data. They also reported the improved survival after liver transplantation due to hepatitis C for patients receiving sirolimus rather than calcineurin inhibitor-based regimens.
In the literature there have already been reported good virological control of HCV among liver transplant recipients after conversion to SRL and the reduction of hepatitis C virus recurrence (GALLEGO et al., 2009; BENEDETTOET al., 2010).
Everolimus has shown a potent inhibitor of mTOR and has been widely used as an immunosuppressive agent in kidney transplant, but no reported effects on HCV progression was found in the literature.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01469884
|Irmandade Da Santa Casa de Misericórdia de Porto Alegre|
|Porto Alegre, Rio Grande Do Sul, Brazil, 90020090|
|Principal Investigator:||Valter Garcia, Physician||IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE|
|Study Chair:||ELIZETE KEITEL, Physician||IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE|
|Study Director:||MARIANA F RODRIGUES, PHARMACIST||IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE|
|Study Director:||DIEGO GNATTA, PHARMACIST||IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE|
|Study Director:||LARISSA S PACHECO, PHARMACIST||IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE|
|Study Director:||BRUNA D CARDOSO, PHARMACIST||IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE|
|Study Director:||RONIVAN L DAL PRA, PHARMACIST||IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE|