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

Phase 4

Completed

• Conditions: BK Virus Nephropathy After Kidney Transplantation
• Interventions: Drug: everolimus

• Registration Number: NCT03216967
• Lead Sponsor: University Hospital, Strasbourg, France

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-04
• Study First Submitted QC: 2017-07-11
• Study First Posted: 2017-07-13
• Study Start: 2018-01-15
• Status Verified: 2024-08
• Primary Completion: 2024-08-01
• Study Completion: 2024-08-01
• Last Update Submitted: 2024-08-16
• Last Update Posted: 2024-08-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IS lowering alone	everolimus	50% decrease of the dose of mycophenolic acid at M1 (target AUC 20 mg.h/L)
Everolimus + IS lowering	everolimus	Stop mycophenolate acid (Cellcept or myfortic) Introduction of everolimus : 2 x 0.75 mg/d per os in patiens treated by ciclosporine

Primary Outcome Measures

Name	Time	Method
The main objective of our study is to evaluate the proportion of patients with BKV clearance 6 months after introduction of everolimus in kidney recipients who develop BKV viremia compared to patients managed with IS reduction alone	6 months after randomization	The primary end point is the proportion of patients with clearance of BK viremia assessed by blood PCR and functional graft 6 months after modification of immunosuppressive therapy

Trial Locations

Locations (14)

CHU - Hôpital Dupuytren; 🇫🇷 Limoges, France

CHRU d'Angers; 🇫🇷 Angers, France

CHU - Hôpital Sud; 🇫🇷 Amiens, France

CHU - Hôpital de la Cavale Blanche; 🇫🇷 Brest, France

AP-HP Hôpital Necker; 🇫🇷 Paris, France

Hôpital Edouard Herriot; 🇫🇷 Lyon, France

CHU Hôpital Gabriel Montpied; 🇫🇷 Clermont-Ferrand, France

CHU Côte de Nacre; 🇫🇷 Caen, France

CHU - Hôpital Maison Blanche; 🇫🇷 Reims, France

CHU Poitiers - Hôpital Jean Bernard; 🇫🇷 Poitiers, France

CHU Rennes - Hôpital Pontchaillou; 🇫🇷 Rennes, France

AP-HP - Hôpital Georges Pompidou; 🇫🇷 Paris, France

Les Hôpitaux Universitaires; 🇫🇷 Strasbourg, France

CHRU - Hôpital Bretonneau; 🇫🇷 Tours, France