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

NCT ID: NCT03216967

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-15
• Study Completion Date: 2024-08-01

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.

Conditions

BK Virus Nephropathy After Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IS lowering alone

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

Group Type: ACTIVE_COMPARATOR

everolimus

Intervention Type: DRUG

Patients with viremia above 2.8 log of copies/ml will be randomized (ratio 1:1) into either of 2 groups Group 1 : control group : immunosuppression lowering or Group 2 : experimental group : immunosuppression lowering and replacement of mycophenolate acid by everolimus Evolution of BKV viremia and allograft function will be assessed during 2 years after randomization

Everolimus + IS lowering

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

Group Type: EXPERIMENTAL

everolimus

Intervention Type: DRUG

Patients with viremia above 2.8 log of copies/ml will be randomized (ratio 1:1) into either of 2 groups Group 1 : control group : immunosuppression lowering or Group 2 : experimental group : immunosuppression lowering and replacement of mycophenolate acid by everolimus Evolution of BKV viremia and allograft function will be assessed during 2 years after randomization

Interventions

everolimus

Patients with viremia above 2.8 log of copies/ml will be randomized (ratio 1:1) into either of 2 groups Group 1 : control group : immunosuppression lowering or Group 2 : experimental group : immunosuppression lowering and replacement of mycophenolate acid by everolimus Evolution of BKV viremia and allograft function will be assessed during 2 years after randomization

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU - Hôpital Sud

Amiens, , France

CHRU d'Angers

Angers, , France

CHU - Hôpital de la Cavale Blanche

Bois-Guillaume, , France

CHU - Hôpital de la Cavale Blanche

Brest, , France

CHU Côte de Nacre

Caen, , France

CHU Hôpital Gabriel Montpied

Clermont-Ferrand, , France

CHU - Hôpital Dupuytren

Limoges, , France

Hôpital Edouard Herriot

Lyon, , France

AP-HP Hôpital Necker

Paris, , France

AP-HP - Hôpital Georges Pompidou

Paris, , France

CHU Poitiers - Hôpital Jean Bernard

Poitiers, , France

CHU - Hôpital Maison Blanche

Reims, , France

CHU Rennes - Hôpital Pontchaillou

Rennes, , France

Les Hôpitaux Universitaires

Strasbourg, , France

CHRU - Hôpital Bretonneau

Tours, , France

Countries

France

References

Caillard S, Meyer N, Solis M, Bertrand D, Jaureguy M, Anglicheau D, Ecotiere L, Buchler M, Bouvier N, Schvartz B, Rerolle JP, Heng AE, Couzi L, Duveau A, Morelon E, LeMeur Y, Golbin L, Thervet E, Benotmane I, Fafi-Kremer S. Insights from the BKEVER Trial comparing everolimus versus mycophenolate mofetil for BK Polyomavirus infection in kidney transplant recipients. Kidney Int. 2025 Feb;107(2):338-347. doi: 10.1016/j.kint.2024.09.018. Epub 2024 Oct 28.

Reference Type: BACKGROUND

PMID: 39490986 (View on PubMed)

Other Identifiers

6646

Identifier Type: -

Identifier Source: org_study_id