Multicenter Clinical Trial to Evaluate the Efficacy of a Preventive Strategy Against CMV Infection in Heart Transplant Patients, Based on the Specific T Cells Response

NCT ID: NCT04278547

Last Updated: 2020-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

188 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-12

Study Completion Date

2023-03-25

Brief Summary

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This study evaluates the efficacy and safety of an individualized preventive strategy against CMV infection in CMV seropositive heart transplant patients based on the specific basal response of the lymphocytes againts CMV (ELISPOT Interferon-γ assay).

In two thirds of the patients a preventive strategy will be carried out based on the result of the ELISPOT IFN-γ assay and in one third of the patients the standard of care strategy will be carried out (universal prophylaxis).

Detailed Description

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Background: The prevention of Cytomegalovirus (CMV) infection in cardiac transplant patients is currently based exclusively on the performance of the serotypes of the receptor and the donor. Despite prophylactic treatment with valganciclovir or preemptive therapy through serial monitoring of blood viral copies, the rate of infection or CMV disease remains high and has a negative clinical impact. The evaluation of the specific T lymphocytes cellular immune response against 2 CMV antigens prior to kidney transplantaction, using the ELISPOT IFN-γ assay discriminates in a better way which patients will develop CMV infection.

Objetives: To compare the cumulative incidence of CMV infection during the first year post-heart transplant amongst CMV seropositive recipients in 12 national centers, where the prophylactic strategy regarding CMV infection will be guided by the ELISPOT IFN-γ assay or not (control). Main variable: number of patients who have CMV infection in the first year post-trasplant (HT).

Hyphotesis: A preventive strategy against CMV infection in CMV seropositive heart transplant patients, based on the specific basal response of the T lymphocytes against CMV, ELISPOT IFN-γ assay, is effective, safe and not inferior than the control group in terms of infection CMV rates. Design: The investigators propose a phase IV clinical trial (with authorized treatment), randomized (2:1), controlled, open label and multicentric, with two parallel groups (Experimental group: preventive strategy based on the ELISPOT IFN-γ result: If patients are stratified as high risk they will receive prophylaxis with valgancyclovir for 3 months and if they are stratified as low risk they will be treated with preemptive therapy guided by CMV polymerase chain reaction analysis; Control group: Standard of care, universal prophylaxis with valgancyclovir for 3 months).

Follow-up: 1 year. Duration of the trial: 3 years. Sample size: 188 patients.

Conditions

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Heart Transplant Infection CMV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase IV clinical trial (with authorized treatment), randomized (2:1), controlled, open label and multicentric, with two parallel groups (Experimental group: preventive strategy based on the ELISPOT IFN-γ result: If patients are stratified as high risk they will receive prophylaxis with valgancyclovir for 3 months and if they are stratified as low risk they will be treated with preemptive therapy guided by CMV polymerase chain reaction analysis; Control group: Standard of care, universal prophylaxis with valgancyclovir for 3 months).
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Experimental group

Preventive strategy based on the ELISPOT IFN-γ result: If patients are stratified as high risk they will receive prophylaxis with valgancyclovir for 3 months and if they are stratified as low risk they will be treated with preemptive therapy guided by CMV polymerase chain reaction analysis;

Group Type EXPERIMENTAL

ELISPOT IFN-γ assay

Intervention Type DIAGNOSTIC_TEST

ELISPOT IFN-γ diagnostic test: Evaluation of specific cellular immune response against the IE-1 antigen and the CMV pp65, using the technique ELISPOT IFN-γ and individualize the preventive strategy according to the result. In patients with a ELISPOT of "low risk" will be made advance therapy (preemptive therapy) guided by PCR of CMV In patients with a "high risk" ELISPOT, universal prophylaxis with valganciclovir will be performed oral (900 mg / 24h) or intravenous ganciclovir (5-10 mg / Kd / day) in case the oral route is not available.

Control group

Standard of care, universal prophylaxis with valgancyclovir for 3 months).

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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ELISPOT IFN-γ assay

ELISPOT IFN-γ diagnostic test: Evaluation of specific cellular immune response against the IE-1 antigen and the CMV pp65, using the technique ELISPOT IFN-γ and individualize the preventive strategy according to the result. In patients with a ELISPOT of "low risk" will be made advance therapy (preemptive therapy) guided by PCR of CMV In patients with a "high risk" ELISPOT, universal prophylaxis with valganciclovir will be performed oral (900 mg / 24h) or intravenous ganciclovir (5-10 mg / Kd / day) in case the oral route is not available.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Valganciclovir

Eligibility Criteria

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Inclusion Criteria

* Adult patients (18 years or more), both sexes, heart transplant patients.
* Patients with positive IgG against CMV (seropositive).
* Informed consent given by the subject or his legal representative.
* Availability of obtaining recipient and donor serologies.
* Availability of obtaining biological samples of peripheral blood post-transplant to be able to perform the ELISPOT IFN-γ assay.
* Women of childbearing age who use effective contraceptive measures during and until, so less, 30 days after treatment. Men who use contraceptive measures of barrier during and for at least 90 days after treatment, unless there is certainty that the female partner does not run the risk of becoming pregnant.

Exclusion Criteria

* Pregnancy and / or breastfeeding period.
* Patients with contraindication for the use of valganciclovir or ganciclovir.
* Patients receiving thymoglobulin as induction therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role collaborator

Spanish Society of Cardiology

OTHER

Sponsor Role collaborator

Hospital Universitari de Bellvitge

OTHER

Sponsor Role lead

Responsible Party

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Elena García Romero

Elena García Romero

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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José González Costello

Role: PRINCIPAL_INVESTIGATOR

Cardiologist

Locations

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Hospital Universitari de Bellvitge

Barcelona, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Jose González Costello

Role: CONTACT

Phone: +0034 932607686

Email: [email protected]

Elena García Romero

Role: CONTACT

Email: [email protected]

Facility Contacts

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Jose González Costello

Role: primary

Other Identifiers

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PI19/01610

Identifier Type: -

Identifier Source: org_study_id