Clinical trial NCT03216967: Multicenter Randomized Two-arms Study Evaluating the BK Viral Clearance in Kidney Transplant Recipients With BK Viremia.
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: BK Virus Nephropathy After Kidney Transplantation
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2017-07-13
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: 6 months after randomization
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU - Hôpital Sud
city: Angers
country: France
facility: CHRU d'Angers
city: Bois-guillaume
country: France
facility: CHU - Hôpital de la Cavale Blanche
city: Brest
country: France
facility: CHU - Hôpital de la Cavale Blanche
city: Caen
country: France
facility: CHU Côte de Nacre
city: Clermont-Ferrand
country: France
facility: CHU Hôpital Gabriel Montpied
city: Limoges
country: France
facility: CHU - Hôpital Dupuytren
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Paris
country: France
facility: AP-HP Hôpital Necker
city: Paris
country: France
facility: AP-HP - Hôpital Georges Pompidou
city: Poitiers
country: France
facility: CHU Poitiers - Hôpital Jean Bernard
city: Reims
country: France
facility: CHU - Hôpital Maison Blanche
city: Rennes
country: France
facility: CHU Rennes - Hôpital Pontchaillou
city: Strasbourg
country: France
facility: Les Hôpitaux Universitaires
city: Tours
country: France
facility: CHRU - Hôpital Bretonneau
Study officials:
References: