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

NCT03216967 | Completed Phase 4

• 1 other identifier: 6646
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 15

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

Outcome Measures

Primary Outcomes (1)

• 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

  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

  6 months after randomization

Study Arms (2)

IS lowering alone

ACTIVE COMPARATOR

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

Drug: everolimus

Everolimus + IS lowering

EXPERIMENTAL

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

Drug: everolimus

Interventions

everolimus 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; IS lowering alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (15)

CHU - Hôpital Sud

Amiens, 80054, France

Location

CHRU d'Angers

Angers, 49033, France

Location

CHU - Hôpital de la Cavale Blanche

Bois-Guillaume, 76230, France

Location

CHU - Hôpital de la Cavale Blanche

Brest, 29609, France

Location

CHU Côte de Nacre

Caen, 14033, France

Location

CHU Hôpital Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

CHU - Hôpital Dupuytren

Limoges, 87042, France

Location

Hôpital Edouard Herriot

Lyon, 69003, France

Location

AP-HP Hôpital Necker

Paris, 75743, France

Location

AP-HP - Hôpital Georges Pompidou

Paris, 75908, France

Location

CHU Poitiers - Hôpital Jean Bernard

Poitiers, 86021, France

Location

CHU - Hôpital Maison Blanche

Reims, 51092, France

Location

CHU Rennes - Hôpital Pontchaillou

Rennes, 35033, France

Location

Les Hôpitaux Universitaires

Strasbourg, 67000, France

Location

CHRU - Hôpital Bretonneau

Tours, 37044, France

Location

Related Publications (1)

• 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.

  PMID: 39490986 BACKGROUND

MeSH Terms

Interventions

Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2017
• First Posted: July 13, 2017
• Study Start: January 15, 2018
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (15)