Multicenter Randomized Two-arms Study Evaluating the BK Viral Clearance in Kidney Transplant Recipients With BK Viremia. (BK EVER)

University Hospital, Strasbourg, France

Status and phase: Completed; Phase 4

Conditions: BK Virus Nephropathy After Kidney Transplantation

Treatments: Drug: everolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT03216967

6646

Details and patient eligibility

About

BK virus nephropathy (BKVN), a consequence of the strong immunosuppressive therapy given after kidney transplantation, represents a growing problem in the kidney transplant (KT) setting. In recent cohorts, BKVN concerns up to 10% of kidney transplant recipients and early signs of BK virus (BKV) infection as development of asymptomatic viruria and viremia are even much more frequent (40% and 20% of patients, respectively). In this context, finding strategies to prevent BKV infection or treat patients before the occurrence of BKV nephropathy is challenging. For several years, detection of BKV replication by real-time PCR in urine and/or blood of kidney transplant recipients at early stages of infection allowed adaptation of their therapy. As BKV reactivates essentially in patients with over-immunosuppression, the first step of the treatment is the reduction of immunosuppression. However, reducing immunosuppression (IS) can lead to acute rejection and allograft loss. Other treatments have been proposed (cidofovir, quinolones) but their toxicity profile or their lack of clinical efficacy are now demonstrated. Hence, an efficient and safe strategy against uncontrolled BKV replication is urgently needed. MTor-inhibitors are well known immunosuppressive drugs used in organ transplantation to prevent graft-rejection. They have furthermore anti-viral effects that can be beneficial for prevention of viral infections after transplantation. Recent evidence that inhibition of mTor pathway had an impact on BK infected cells provides additional insight into the observed benefits associated with these drugs. The aim of our study is to evaluate the effect of the mTor inhibitor everolimus on the prevention of severe BKV infection (BKV nephropathy or loss of the allograft) after kidney transplantation compared to the reduction of immunosuppression alone in kidney recipients with BK viremia.

Enrollment: 130 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients
• Kidney transplant recipients
• Patients treated by a calcineurin inhibitor and mycophenolic acid
• Viremia >= 2.8 log UI/ml
• Patients who have given written informed consent
• Negative pregnancy test (blood β-HCG dosage)

Exclusion criteria

• Known proved BKV nephropathy
• Hypersensitivity to everolimus, sirolimus or excipient
• Concomitant treatment by leflunomide, cidofovir, sirolimus, Millepertuis (Hypericum Perforatum)
• Pregnant or lactating women
• Women of child bearing potential unless they are using a birth control method

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

IS lowering alone

Active Comparator group

Description:

50% decrease of the dose of mycophenolic acid at M1 (target AUC 20 mg.h/L)

Treatment:

Drug: everolimus

Everolimus + IS lowering

Experimental group

Description:

Stop mycophenolate acid (Cellcept or myfortic) Introduction of everolimus : 2 x 0.75 mg/d per os in patiens treated by ciclosporine

Treatment:

Drug: everolimus