Effectiveness of an Immune-guided Cytomegalovirus Infection Preventive Strategy Compared to a Universal Prophylactic Strategy in Renal Transplant Patients (CYTOPREV)

University Hospital, Rouen

Status and phase: Not yet enrolling; Phase 3

Conditions: Kidney Transplant Infection

Treatments: Drug: ROVALCYTE

Study type: Interventional

Funder types: Other

Identifiers

NCT05708508

2020/0422/HP

Details and patient eligibility

About

Cytomegalovirus (CMV) establishes a chronic infection in 60% of the general population. In renal transplant recipients, it is responsible for morbidities occurring mainly in the first 6 months after transplantation. These include viral reactivations linked to immunosuppressive treatment inhibiting the anti-CMV T lymphocyte response. CMV infection, a sign of uncontrolled viral replication, is defined by the detection of viral DNA in the peripheral blood (DNAemia). CMV disease is defined as the association of an infection and symptoms attributable to the virus.

In transplant recipients carrying the virus before transplantation (positive serology: CMV+), two infection prevention strategies are recommended: either close monitoring of DNAemia with antiviral treatment in the event of positive detection (pre-emptive strategy), or antiviral treatment for the first 3 months following the transplant (prophylactic strategy). Both strategies result in the occurrence of CMV infection in 15 to 20% of patients within the first 6 months, with the majority of events occurring between 3 and 6 months.

Numerous studies show that the evaluation of the anti-CMV T lymphocyte response, either before (D0) or early after transplantation (D15), or when antiviral prophylaxis is stopped, allows the identification of patients at risk of CMV infection. No study has yet demonstrated the contribution of such an evaluation in a preventive strategy. We therefore propose such a study.

Enrollment: 144 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Renal transplant patient for 1 to 12 days
• CMV seropositivity on the day of transplantation: IgG threshold =6 AU/mL CMIA CMV IgG, Architect i4000 (Abbott)) (Serology performed on D0, before the transplant)
• Non-depleting inducing immunosuppressive treatment (Basiliximab) (implementation before the transplant)
• Affiliation to a social security scheme
• Patient having read and understood the information letter and signed the consent form

Exclusion criteria

• Active CMV infection (detectable CMV DNAemia - peripheral CMV DNAemia ≥ 305 IU/mL)
• Patient with hypersensitivity to valganciclovir, ganciclovir, aciclovir or valaciclovir or to any of the excipients
• Lympho-depleting inducing immunosuppressive treatment (antithymoglobulins)
• Neutropenia (neutrophils < 500/mm3) or thrombocytopenia (platelets < 25,000/mm3) or anemia (hemoglobin < 8G/L) identified on routine care samples taken on the day of inclusion

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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144 participants in 2 patient groups

"Immuno-guided strategy" arm

Experimental group

Description:

* Patients in the "low risk" group will be monitored between D+15 and W+28 according to a strategy preemptive. * Patients in the "high risk" group (anti-CMV response \<130 SFC/106 cells) will be treated according to the terms of the "universal prophylaxis" arm from D+15 and until W+15. At the W+15 visit: * If the patient is considered at "low risk", the antiviral treatment is stopped and he will continue the follow-up according to the modalities of the "universal prophylaxis" arm until W+28. * If the patient is still at "high risk" antiviral treatment will be continued until W+28.

Treatment:

Drug: ROVALCYTE

"Universal prophylaxis" arm

Active Comparator group

Description:

Patients will receive from D+15 post-transplant an antiviral treatment with valganciclovir (ROVALCYTE) for the first 3 months following the transplant. Clinico-biological monitoring during the 6 months according to the usual practices of the 2 centers and monitoring of CMV DNAemia.

Treatment:

Drug: ROVALCYTE