De Novo Everolimus-based Therapy for Renal Transplantation Using Rituximab Induction

Renal Insufficiency Clinical Trial

Official title: Clinical Outcome of de Novo Everolimus-based Immunosuppressive Therapy for Renal Transplantation Using Rituximab Induction

Status Terminated

Clinical Trial Summary

The investigators hypothesized that everolimus-based immunosuppressive therapy combined with rituximab induction could provide comparable safety profiles for renal transplant patients, as compared to standard immunosuppressive therapy using thymoglobulin induction, tacrolimus, mycophenolate mofetil and steroids, in terms of acute rejection rate and renal function.

Rituximab was reported to reverse refractory acute kidney transplant rejection. Combined with immunoadsorption with or without IVIG, rituximab could successfully prevent antibody-mediated rejection in ABO-incompatible renal transplantation. This study is to assess whether a CNI-free regimen including B-cell depleting antibody induction, everolimus and MMF results in comparable long-term function without a negative impact on safety or efficacy of immunosuppression. This study will be open-label and two-arm randomized (2:1).

Clinical Trial Description

Patients of the study arm (2/3 of the patients) will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months. All patients will receive mycophenolate mofetil (MMF) starting at 2 g/d in divided doses, and then adjusted to maintain WBC between 4000~6000/mm3. All patients entering this study will receive co-trimoxazole as prophylactic medication for at least 12 weeks post-operatively. Valgancyclovir will be given for anti-viral prophylaxis. During the transplant operation, renal biopsy will be performed before vascular perfusion for baseline pathology, and a follow-up biopsy will be scheduled at 2 years after transplantation. The primary endpoint will be incidence of acute rejection, and the secondary endpoints include renal function, graft and patient survival.

Male and female adult patients who are to receive renal transplantation may enter the study. The intention is to enroll 90 patients who have fulfilled inclusion/exclusion criteria into the study. Sixty patients will receive rituximab and everolimus-based therapy, but the other thirty patients will receive thymoglobulin and tacrolimus-based therapy. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Renal Insufficiency

• NCT number: NCT01312064
• Study type: Interventional
• Source: National Taiwan University Hospital
• Status: Terminated
• Phase: Phase 4
• Start date: April 2011
• Completion date: April 2012