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

Primary Purpose

BK Virus Nephropathy After Kidney Transplantation

Status
Active
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
everolimus
Sponsored by
University Hospital, Strasbourg, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for BK Virus Nephropathy After Kidney Transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • CHU - Hôpital Sud
  • CHRU d'Angers
  • CHU - Hôpital de la Cavale Blanche
  • CHU - Hôpital de la Cavale Blanche
  • CHU Côte de Nacre
  • CHU Hôpital Gabriel Montpied
  • CHU - Hôpital Dupuytren
  • Hôpital Edouard Herriot
  • AP-HP Hôpital Necker
  • AP-HP - Hôpital Georges Pompidou
  • CHU Poitiers - Hôpital Jean Bernard
  • CHU - Hôpital Maison Blanche
  • CHU Rennes - Hôpital Pontchaillou
  • Les Hôpitaux Universitaires
  • CHRU - Hôpital Bretonneau

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

IS lowering alone

Everolimus + IS lowering

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 4, 2017
Last Updated
August 18, 2023
Sponsor
University Hospital, Strasbourg, France
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1. Study Identification

Unique Protocol Identification Number
NCT03216967
Brief Title
Multicenter Randomized Two-arms Study Evaluating the BK Viral Clearance in Kidney Transplant Recipients With BK Viremia.
Acronym
BK EVER
Official Title
Multicenter Randomized Two-arms Study Evaluating the BK Viral Clearance in Kidney Transplant Recipients With BK Viremia After Reduction of Immunosuppression Alone vs. Reduction of Immunosuppression and Replacement of Mycophenolate Mofetil by Everolimus
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 15, 2018 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
BK Virus Nephropathy After Kidney Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IS lowering alone
Arm Type
Active Comparator
Arm Description
50% decrease of the dose of mycophenolic acid at M1 (target AUC 20 mg.h/L)
Arm Title
Everolimus + IS lowering
Arm Type
Experimental
Arm Description
Stop mycophenolate acid (Cellcept or myfortic) Introduction of everolimus : 2 x 0.75 mg/d per os in patiens treated by ciclosporine
Intervention Type
Drug
Intervention Name(s)
everolimus
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
6 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
CHU - Hôpital Sud
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CHRU d'Angers
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
CHU - Hôpital de la Cavale Blanche
City
Bois-guillaume
ZIP/Postal Code
76230
Country
France
Facility Name
CHU - Hôpital de la Cavale Blanche
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
CHU Côte de Nacre
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
CHU Hôpital Gabriel Montpied
City
Clermont-Ferrand
ZIP/Postal Code
63000
Country
France
Facility Name
CHU - Hôpital Dupuytren
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Hôpital Edouard Herriot
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
AP-HP Hôpital Necker
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
AP-HP - Hôpital Georges Pompidou
City
Paris
ZIP/Postal Code
75908
Country
France
Facility Name
CHU Poitiers - Hôpital Jean Bernard
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
CHU - Hôpital Maison Blanche
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
CHU Rennes - Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Les Hôpitaux Universitaires
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Name
CHRU - Hôpital Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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