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 (ELISPOT-TC)

Phase IV Clinical Trial, Open, Randomized, Controlled and Multicentric, With Two Parallel Groups, to Assess the Efficacy of a Preventive Strategy Against Cytomegalovirus Infection in Heart Transplant Patients, Based on the Specific Basal T Cell Response Against Cytomegalovirus: ELISPOT-TC

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).

Study Overview

• Status: Recruiting
• Conditions: CMV Infection; Heart Transplant Infection
• Intervention / Treatment: Diagnostic test: ELISPOT IFN-γ assay

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 188
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jose González Costello; Phone Number: +0034 932607686; Email: jgonzalez@bellvitgehospital.cat
• Study Contact Backup: Name: Elena García Romero; Email: e.garcia.r@bellvitgehospital.cat

Study Locations

• Spain
  • Barcelona, Spain, 08907
    • Recruiting
    • Hospital Universitari de Bellvitge
    • Contact: Jose González Costello; Email: jgonzalez@bellvitgehospital.cat
    • Sub-Investigator: Elena García Romero

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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;	Diagnostic test: 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.; Other Names: Valganciclovir
No Intervention: Control group; Standard of care, universal prophylaxis with valgancyclovir for 3 months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who have CMV infection in the first year post heart transplant.	Any viremia	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with late CMV infection.	Number of patients with late CMV infection who have received prophylaxis with valganciclovir or ganciclovir (group 1 a and control group), once the treatment is finished.	One year
Number of patients with acute rejection.		One year
Number of patients with vascular graft disease.		One year
Number of patients with other bacterial or viral opportunistic infections.		One year
Number of patients with leukopenia secondary to prophylaxis.		One year
Number of patients with neutropenia secondary to prophylaxis.		One year
Number of leukopenia patients presenting with other bacterial infections or viral.		One year
Number of deceased patients during hospital admission post-heart transplant.		One year
Number of deceased patients, related to CMV infection, in the first year post-transplant.		One year
Number of deceased patients, related to CMV disease, in the first post-transplant year.		One year
Number of patients who died from any cause in the first year post-heart transplant.		One year
Title of specific Inmunoglobulin G antibodies against serum CMV.		One year
Title of nonspecific serum gammaglobulins.		One year
CMV-specific memory response B (ELISPOT B).		One year
Number of patients whose ELISPOT varies from low to intermediate or high risk.		One year
Number of patients whose ELISPOT varies from intermediate or high risk to low risk.		One year
Number of spots against the IE-1 antigen.		One year
Number of spots against the pp65 antigen.		One year
Number of copies of CMV DNA measured by polymerase chain reaction (PCR).		One year
Estimate the economic cost of both strategies studied in this clinical trial		One year

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge
• Collaborators: Instituto de Salud Carlos III; Spanish Society of Cardiology
• Investigators: Principal Investigator: José González Costello, Cardiologist

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2020
• Primary Completion (Anticipated): March 25, 2022
• Study Completion (Anticipated): March 25, 2023

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): December 23, 2020
• Last Update Submitted That Met QC Criteria: December 22, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: PI19/01610

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No