Randomized Clinical Trial, Open, Multicenter Parallel, no Suspension Inferiority Prophylactic Treatment With Valganciclovir in Kidney Transplant CMV-seropositive Cellular Immunity to Develop CD8 + CMV-specific Treatment After Induction Thymoglobulin.

Sponsor

Maimónides Biomedical Research Institute of Córdoba (Other)

Overall Status

Completed

CT.gov ID

NCT03123627

Collaborator

(none)

150

Enrollment

Location

Arms

37.9

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hypothesis: Valganciclovir prophylaxis can be discontinued before 3 months in CMV-seropositive renal transplant recipients receiving induction thymoglobulin when developing CMV-specific cellular immunity after transplantation.

Objective Meet the efficacy and safety of valganciclovir prophylaxis suspend in CMV-seropositive kidney transplant recipients with CD8 + cellular immunity CMV-specific transplant, receiving Thymoglobulin induction and maintain cellular immunity-specific CD8 + CMV after transplantation.

Design: noninferiority clinical trial (study A) in CMV-seropositive kidney transplant recipients with CMV-specific cellular immunity pretransplant (Quantiferon reactive CMV) received induction with thymoglobulin

Patients meeting inclusion criteria will be randomized to:

Control Arm: valganciclovir prophylaxis until day +90 as recommended by the International Consensus document of the TTS (Transplantation 2013:96:333-360).
Experimental arm: prophylaxis with valganciclovir and determination of CMV-specific cellular immunity day +15, +30, +45 and +60. Prophylaxis was discontinued when the patient developed CMV-specific cellular immunity. Patients who did not develop CMV specific immunity continue prophylaxis until day +90.

Analysis: The incidence of CMV disease according to the strategy used was calculated using Kaplan-Meier curves that were compared using the log-rank test.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Infection	Drug: New profilaxis Drug: Profilaxis recommended	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Clinical Trial, Open, Multicenter Parallel, no Suspension Inferiority Prophylactic Treatment With Valganciclovir in Kidney Transplant CMV-seropositive Cellular Immunity to Develop CD8 + CMV-specific Treatment After Induction Thymoglobulin.

Actual Study Start Date :

Aug 23, 2016

Actual Primary Completion Date :

Oct 21, 2019

Actual Study Completion Date :

Oct 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: New profilaxis Prophylaxis is discontinued when the patient developed CMV-specific cellular immunity.	Drug: New profilaxis Primary endpoint: incidence of CMV disease at 12 months after transplantation. Study the predictive value of the assay of CD8 + T cell immunity specific for defined CMV-patients in which they can stop prophylaxis. The definition of CMV disease was based on those recommended by the American Society of Trasnplantation for use in clinical trials (Humar A. Am J Transplant 2006; 6:262-74) criteria.
Active Comparator: Profilaxis recommended by TTS Valganciclovir prophylaxis until day +90 as recommended by the International Consensus document of the TTS.	Drug: Profilaxis recommended Secondary end points: percentage of patients developing T cell immunity in CMV-specific transplantation after receiving timoglubulina induction and valganciclovir prophylaxis. T cell development inmnunidad CD8 + CMV-specific is defined as production of γ> 0.2 interferon by CD8 + T cells stimulated by CMV-specific CMV antigens (QF reagent).

Arm

Intervention/Treatment

Experimental: New profilaxis

Prophylaxis is discontinued when the patient developed CMV-specific cellular immunity.

Drug: New profilaxis

Primary endpoint: incidence of CMV disease at 12 months after transplantation. Study the predictive value of the assay of CD8 + T cell immunity specific for defined CMV-patients in which they can stop prophylaxis. The definition of CMV disease was based on those recommended by the American Society of Trasnplantation for use in clinical trials (Humar A. Am J Transplant 2006; 6:262-74) criteria.

Active Comparator: Profilaxis recommended by TTS

Valganciclovir prophylaxis until day +90 as recommended by the International Consensus document of the TTS.

Drug: Profilaxis recommended

Secondary end points: percentage of patients developing T cell immunity in CMV-specific transplantation after receiving timoglubulina induction and valganciclovir prophylaxis. T cell development inmnunidad CD8 + CMV-specific is defined as production of γ> 0.2 interferon by CD8 + T cells stimulated by CMV-specific CMV antigens (QF reagent).

Outcome Measures

Primary Outcome Measures

Incidence of CMV disease at 12 months after transplantation [12 months]
Incidence of CMV disease at 12 months after transplantation. Study the predictive value of the assay of CD8 + T cell immunity specific for defined CMV-patients in which they can stop prophylaxis. The definition of CMV disease was based on those recommended by the American Society of Trasnplantation criteria for use in clinical trials

Secondary Outcome Measures

Percentage of patients who recover CMV-specific CD8+ T-cell immunity in the posttransplantation period after receiving thymoglobulin induction therapy and valganciclovir prophylaxis [12 months]
CMV-specific CD8+ T-cell immunity will be defined using the QF-CMV technique as IFN-γ production equal to or greater than 0.2 IU/mL following stimulation of CD8+ T cells by CMV antigens (QF-CMV "Reactive").CMV replication was considered asymptomatic when it was not accompanied by CMV disease (CMV syndrome or CMV disease)
Incidence of CMV replication [12 months]
CMV replication was defined as >1500 IU/mL in plasma or >5000 IU/mL in whole blood. CMV replication was considered asymptomatic when it was not accompanied by CMV disease (CMV syndrome or CMV disease)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Renal transplant CMV-Seropositive
CD8+ Tcell CMV especific pretransplant (CMV-reactive quantiferon pretrasplant)
18 years (adult)
Receiving Thymoglobulin induction therapy
Receiving Valganciclovir prophylaxis
Written informed consent for trial entry

Exclusion Criteria:

Multivisceral transplants including kidney-pancreas.
HIV-infected Patients
Patients who can not comply with the monitoring protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hosìtal Universitario Reina Sofia	Córdoba		Spain	14004

Sponsors and Collaborators

Maimónides Biomedical Research Institute of Córdoba

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Maimónides Biomedical Research Institute of Córdoba

ClinicalTrials.gov Identifier:

NCT03123627

Other Study ID Numbers:

TIMOVAL

First Posted:

Apr 21, 2017

Last Update Posted:

Feb 2, 2021

Last Verified:

Jan 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Maimónides Biomedical Research Institute of Córdoba

Cytomegalovirus, Seropositive

Study Results

No Results Posted as of Feb 2, 2021