Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T Cells Immunomonitoring.

Kidney Transplant Infection Clinical Trial

— SPARCKLING  

Official title:

Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03339661
• Other study ID #: CHUBX 2016/40
• Status: Completed
• Phase: Phase 2
• Start date: November 23, 2017
• Est. completion date: November 23, 2020

Study information

• Verified date: June 2021
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In kidney transplant patients, CMV infection remains the leading infectious cause of morbidity and mortality. Clinical and virological relapses are common and are involved in chronic graft dysfunction. To date, it is not certain that secondary prophylaxis allows reducing these relapses, although this prophylaxis is part of the current recommendations. Our team has recently shown that the expansion of γδ T cells in peripheral blood during CMV infection was correlated with the absence of virological and clinical relapses. Indeed, the absence of relapse was associated in 94.7% of cases with the presence of γδ T cells expansion while relapses occurred in about 90% of cases in the absence of γδ T cells expansion. These results suggest that the indication and duration of secondary prophylaxis after the curative treatment of CMV infection in kidney transplantation could be guided by the immune surveillance of γδ T cells.

Description:

The study aim to demonstrate that the expansion of γδ T cells at the end of curative treatment predicts the absence of virological and clinical relapses. This is a pilot study that will be conducted in the transplant center of Bordeaux and Lyon. After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of γδ T cells immunomonitoring:

(I) Secondary prophylaxis will not be started in patients with γδ T cell expansion at the end of curative treatment (group 1) (II) Secondary prophylaxis will be initiated in patients who have not γδ T cell expansion and will continue for 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A. Patients who still not had γδ T cells expansion during or at the end of secondary prophylaxis will compose the group 2B.

The primary outcome of this study will be to evaluate the occurrence of virological relapse, assessed by monitoring CMV ADNemia, at one year of a first CMV disease, in kidney transplant patients, with secondary prophylaxis based on the monitoring of γδ T cells.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: November 23, 2020
• Est. primary completion date: November 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female over 18 years old without weight or ethnicity criteria, kidney transplant.

• Patient affiliated or beneficiary of a social security scheme.

• Patient with symptomatic or non-symptomatic CMV infection requiring curative treatment with ganciclovir or valganciclovir.

• Free, informed and written consent signed by the participant and the investigator (at the latest, on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

• Resistance documented to antivirals.

• Hemodialysis patient.

• Number of polymorphonuclear neutrophils less than 500 / µL and / or number of platelets less than 25,000 / µL, and / or lower hemoglobin 8 g / dL.

• Contraindication to valganciclovir, including known hypersensitivity to valganciclovir and / or aciclovir and / or valaciclovir or ganciclovir or their excipients, known severe intolerance to valganciclovir or ganciclovir.

• Women of childbearing age without a negative pregnancy test at baseline and without effective contraception (estrogen-progestin, intrauterine device) throughout the study period and two months after cessation of the follow-up period.

• Nursing women.

• Men without mechanical contraception during treatment and for at least 90 days after treatment.

• Ongoing participation in another clinical trial evaluating a drug. Participation in an observational study will not be considered a contraindication.

• The patient's foreseeable inability to comply with planned visits in the protocol.

• Non-negativation of CMV PCR at 8 weeks

Related Conditions & MeSH terms

• Infection
• Kidney Transplant Infection

Intervention

Drug:
• Group 1_No proph treatment
After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of ?d T cells immunomonitoring. In this group, expansion of ?d T cell at the end curative treatment was detected, so secondary prophylaxis will not be started.
• Group 2A_Proph treatment and ?d T cell expansion
After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of ?d T cells immunomonitoring. In this group, ?d T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue during 3 months maximum. The occurrence of ?d T cells expansion during or at the end of secondary prophylaxis will define the group 2A.
• Group 2B_Proph treatment and no ?d T cell expansion
After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of ?d T cells immunomonitoring. In this group, ?d T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue during 3 months maximum. Patients who still not had ?d T cells expansion during or at the end of secondary prophylaxis will compose the group 2B.

Locations

Country	Name	City	State
France	Hôpital Pellegrin - CHU de Bordeaux	Bordeaux
France	Hôpital Edouard Herriot - Hospices Civils de Lyon	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of virological relapse occurence	The primary outcome of this study will be to evaluate the occurrence of virological relapse, assessed by monitoring CMV ADNemia.	12 months after inclusion visit
Secondary	Cumulative incidence of clinical recurrence	Cumulative incidence of clinical recurrence defined by a positive CMV PCR associated with clinical and biological signs of CMV disease. This incidence is expressed as a percentage of the total number of patients with CMV infection included.	12 months after inclusion visit
Secondary	?d T cells expansion dynamic	Description of the dynamics of ?d T cells expansion in all patients. At each visit, an immunophenotyping with analysis of the percentage of ?d T cells will be performed.	12 months after the inclusion visit
Secondary	Cumulative incidence of clinical recurrence at discontinuation of prophylaxis.	These incidences will be expressed as a percentage of the total number of patients who have had CMV infection included. Recidivism will be collected by the investigating physician when observed during a follow-up visit.	12 months after the inclusion visit
Secondary	Cumulative incidence of virological recurrence at discontinuation of prophylaxis.	These incidences will be expressed as a percentage of the total number of patients who have had CMV infection included. Recidivism will be collected by the investigating physician when observed during a follow-up visit.	12 months after inclusion visit
Secondary	secondary prophylaxis duration	The duration of the secondary prophylaxis is defined by the duration of treatment since the stop of the curative treatment until the stop of the prophylactic treatment.	12 months after inclusion visit
Secondary	Prophylaxis treatment savings evaluation	Evaluation of prophylaxis treatment savings (compared to a one-month prophylaxis) by number of subject and average total duration (with standard deviation) of treatment.	12 months after inclusion visit
Secondary	Proportion of antiviral resistant infections	the proportion of antiviral resistant infections confirmed by genotypic analysis (mutations UL97 and UL54) sought during recurrence in case of clinical suspicion.	12 months after inclusion visit
Secondary	GFR average	GFR average and its standard deviation are estimated according to MDRD formula	12 months after inclusion visit
Secondary	Compliance rate	The compliance rate will, be performed by a patient notebook.	12 months after inclusion visit