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

NCT ID: NCT05708508

Last Updated: 2023-02-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-31
• Study Completion Date: 2027-06-01

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.

Conditions

Kidney Transplant Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

"Immuno-guided strategy" arm

• 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.

Group Type: EXPERIMENTAL

ROVALCYTE

Intervention Type: DRUG

"Immuno-guided strategy" arm

"Universal prophylaxis" arm

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.

Group Type: ACTIVE_COMPARATOR

ROVALCYTE

Intervention Type: DRUG

"Immuno-guided strategy" arm

Interventions

ROVALCYTE

"Immuno-guided strategy" arm

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Dominique Bertrand

Role: CONTACT

dominique.bertrand@chu-rouen.fr

0232885452

References

Vernooij RW, Michael M, Colombijn JM, Owers DS, Webster AC, Strippoli GF, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2025 Jan 14;1(1):CD005133. doi: 10.1002/14651858.CD005133.pub4.

Reference Type: DERIVED

PMID: 39807668 (View on PubMed)

Other Identifiers

2020/0422/HP

Identifier Type: -

Identifier Source: org_study_id