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

Phase 3

Not yet recruiting

• Conditions: Kidney Transplant Infection
• Interventions: Drug: ROVALCYTE

• Registration Number: NCT05708508
• Lead Sponsor: University Hospital, Rouen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-01
• Study First Submitted: 2023-01-23
• Study First Submitted QC: 2023-01-23
• Last Update Submitted: 2023-01-23
• Study First Posted: 2023-02-01
• Last Update Posted: 2023-02-01
• Study Start: 2023-08-31
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 144

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
"Immuno-guided strategy" arm	ROVALCYTE	* 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.
"Universal prophylaxis" arm	ROVALCYTE	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.

Primary Outcome Measures

Name	Time	Method
Demonstrate, in CMV+ transplant patients, the efficacy of an immuno-guided preventive strategy compared to the universal prophylactic strategy, in terms of CMV infection in the 6 months following kidney transplantation.	6 months	Proportion of patients with CMV infection within 6 months of transplantation.