Use of Tacrolimus and MTOR Inhibitors With Anticipatory Therapy vs. Tacrolimus and Mycophenolic Acid With Universal Prophylaxis in Renal Recipients at High Risk of Posttransplant Cytomegalovirus.

NCT ID: NCT07203664

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-30
• Study Completion Date: 2026-12-31

Brief Summary

The overall objective of this project is to optimise preventive treatment of CMV infection/disease in renal transplant recipients at increased risk of CMV post-transplantation. The specific objectives are: (1) To compare the incidence of CMV infection/disease at 6 months post-transplant in Ig G CMV positive (R+CMV) recipients receiving induction treatment with thymoglobulin and one of the two maintenance immunosuppressive treatment regimens used in routine clinical practice : tacrolimus and MTOR inhibitors (group 1) or tacrolimus and mycophenolic acid (group 2); (2) To monitor CMV-specific cellular immunity before transplantation, at 15, 30 and 90 days post-transplantation. For this purpose, an exploratory phase 4 clinical trial has been designed in which will select 30 R+CMV patients receiving renal transplantation with induction treatment with thymoglobulin. After signing informed consent, patients will be randomised to receive one of the two immunosuppression regimens indicated above. The patients in group 1 will receive early therapy as a CMV prevention strategy and patients in group 2 will receive universal prophylaxis for 3 months. Follow-up visits to will be conducted according to the usual protocol and clinical and virological variables will be collected. In addition, blood samples will be collected for the assessment of CMV-specific cellular immunity before and after transplantation. The primary endpoint is the presence of CMV infection/disease post-renal transplantation at 6 months. Secondary variables include renal function, acute rejection, patient and graft survival and the occurrence of surgical or haematological complications.

Detailed Description

HYPOTHESIS The use of immunosuppressive maintenance therapy including mTOR inhibitors versus the use of mycophenolic acid in kidney transplant patients with an increased risk of post-transplant CMV disease (R+CMV receiving induction with thymoglobulin) will allow optimisation of the preventive treatment of these patients, presenting a similar incidence of post-transplant CMV disease in both groups and better maintenance of CMV-specific cellular immunity post-transplant.

OBJECTIVES General Objective: To improve the preventive treatment of CMV disease in renal transplant patients at increased risk.

Main Objectives: (1) To compare the incidence of CMV disease at 6 months post-renal transplant in Ig G CMV-positive recipients receiving induction treatment with thymoglobulin and maintenance treatment with tacrolimus and mTOR inhibitors (group 1) with CMV prevention strategy of anticipatory therapy or tacrolimus and mycophenolic acid (group 2) with CMV prevention strategy with universal prophylaxis. (2) Monitor CMV-specific cellular immune response before transplantation and at 15, 30 and 90 days post-transplantation in each of the two treatment groups using Quantiferon-CMV.

Secondary Objectives: (3) To compare between the two groups the incidence of CMV infection, delayed initial graft function, acute rejection diagnosed by renal biopsy, renal function and patient and graft survival in the first 6 months post-transplant. (4) To compare between the two groups the presence of surgical (lymphocele requiring intervention) or haematological (neutropenia) complications in the first 6 months post-transplantation.

STUDY DESIGN Phase IV, exploratory, randomised, open-label, single-centre, exploratory clinical trial to evaluate the effectiveness of CMV prevention strategies comparing early therapy vs. universal prophylaxis in Ig G CMV-positive kidney transplant recipients treated with thymoglobulin receiving tacrolimus and mTOR inhibitors (group 1) vs. tacrolimus and mycophenolic acid (group 2).

Patients who meet the inclusion criteria and who sign the informed consent form the day before transplant surgery (pre-transplant day) will have a blood sample taken for CMV-specific cellular immunity analysis using quantiferon CMV and will be randomised into two groups on the day of renal transplant surgery (day 0).

a) Group 1: Will receive, as a CMV prevention strategy, early therapy, and as maintenance immunosuppressive treatment steroids, tacrolimus and mTOR inhibitors. b) Group 2: Will receive, as a CMV prevention strategy, universal prophylaxis, and as maintenance immunosuppressive therapy steroids, tacrolimus and mycophenolic acid. A randomisation list will be generated using SAS 9.4. software, in order to achieve a balanced randomisation in the treatment groups. The ratio will be 1:1 for each group and stratified by sex.

Definition of the groups: Group 1: Will receive early therapy, as a prevention strategy, which consists of starting antiviral treatment with valganciclovir (900 mg/12 hours, adjusted to renal function, according to the technical data sheet) when CMV viral replication is detected in blood above 1,000 copies/ml and treatment will be suspended when the viral load is negative in two consecutive controls.

Group 2: will receive universal prophylaxis with valganciclovir (900 mg/24 hours, adjusted to renal function, according to technical data sheet) during the first 3 months post-transplant, as a CMV prevention strategy.

All patients will receive immunosuppressive induction treatment with thymoglobulin (at least 1 dose and a maximum of 5 doses) and immunosuppressive maintenance treatment with tacrolimus + mTOR inhibitors (patients in group 1) or tacrolimus + mycophenolic acid (patients in group 2) following the guidelines of the technical file and the centre's usual protocols.

Follow-up visits will be performed at 15, 30, 90, 120, 120, 150 and 180 days post-transplant where clinical, analytical, virological (CMV viral loads by PCR in whole blood) and immunological (analysis of CMV-specific cellular immunity by CMV quantiferon) data of the patients will be evaluated. Data on the presence or absence of CMV infection or disease at each visit, concomitant medication changes and adverse events will also be collected.

Conditions

Evaluate the Effectiveness of CMV Prevention Strategies in Kidney Transplant Recipients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

mTOR inhibitors

Preemptive therapy will be administered as a preventive strategy, consisting of initiating antiviral treatment with valganciclovir (900 mg every 12 hours, adjusted according to renal function as per the technical data sheet) when CMV viral replication in blood exceeds 1,000 copies/ml. Treatment will be discontinued once viral load becomes undetectable in two consecutive tests

Group Type: EXPERIMENTAL

steroids, tacrolimus and mTOR inhibitors

Intervention Type: COMBINATION_PRODUCT

Patients receive immunosuppressive induction treatment with thymoglobulin (at least 1 dose and maximum of 5 doses) and immunosuppressive maintenance treatment with tacrolimus + mTOR inhibitors. Preemptive therapy will be administered as a preventive strategy, consisting of initiating antiviral treatment with valganciclovir (900 mg every 12 hours, adjusted according to renal function as per the technical data sheet) when CMV viral replication in blood exceeds 1,000 copies/ml. Treatment will be discontinued once viral load becomes undetectable in two consecutive tests.

Universal prophylaxis

As a preventive strategy against CMV, the patient will receive universal prophylaxis, and for maintenance immunosuppressive treatment, steroids, tacrolimus, and mycophenolic acid will be administered.

Group Type: ACTIVE_COMPARATOR

steroids, tacrolimus and mycophenolic acid.

Intervention Type: COMBINATION_PRODUCT

Patients will receive immunosuppressive induction treatment with thymoglobulin (at least 1 dose and a maximum of 5 doses) and tacrolimus + mycophenolic acid following the guidelines of the technical file and the centre's usual protocols.

Interventions

steroids, tacrolimus and mTOR inhibitors

Patients receive immunosuppressive induction treatment with thymoglobulin (at least 1 dose and maximum of 5 doses) and immunosuppressive maintenance treatment with tacrolimus + mTOR inhibitors. Preemptive therapy will be administered as a preventive strategy, consisting of initiating antiviral treatment with valganciclovir (900 mg every 12 hours, adjusted according to renal function as per the technical data sheet) when CMV viral replication in blood exceeds 1,000 copies/ml. Treatment will be discontinued once viral load becomes undetectable in two consecutive tests.

Intervention Type: COMBINATION_PRODUCT

steroids, tacrolimus and mycophenolic acid.

Patients will receive immunosuppressive induction treatment with thymoglobulin (at least 1 dose and a maximum of 5 doses) and tacrolimus + mycophenolic acid following the guidelines of the technical file and the centre's usual protocols.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• Age 18 years or more.
• Positive pre-transplant Ig G CMV serology.
• Receive immunosuppressive induction treatment with thymoglobulin (between 1 and 5 doses).
• Agree to participate in the study by signing the informed consent form.

Exclusion Criteria

• Patients with negative pre-transplant Ig G CMV serology.
• HIV-infected patients.
• Patients receiving induction therapy with basiliximab.
• Patients who cannot comply with the follow-up protocol.
• Patients who cannot receive iMTOR as initial maintenance immunosuppressive therapy, such as patients with chronic kidney disease secondary to hepatorenal polycystic kidney disease and patients who are expected to undergo complex vascular surgery.
• Patients who for any reason should not be included in the study according to the evaluation of the research team.

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

Sponsors

Hospital Universitario La Paz

OTHER

Sponsor Role: lead

Responsible Party

María Ovidia López Oliva

Dra.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital Universitario La Paz, Pº de la Castellana, 261 (Servicio de Nefrologia)

Madrid, Madrid, Spain

Countries

Spain

Central Contacts

María O. López Oliva, Dra

Role: CONTACT

mlopezo@salud.madrid.org

+34 91 727 70 00

Other Identifiers

TIMTOR

Identifier Type: -

Identifier Source: org_study_id