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Context
Cytomegalovirus (CMV) infection is a frequent and potentially severe event in solid organ transplant (SOT) recipients.
Most of available treatment display adverse effects that limit their use. Therefore, in case of an infection, it is of primary importance to identify the patients at high risk of severe infection and/or disease, and who ill benefit the most from antiviral therapy.
As CMV infection is mainly controlled by cellular immunity, measuring specific anti-CMV T lymphocyte immunity could be an interesting tool for identifying these at-risk individuals. One of these tests is the QuantiFERON-CMV (QF-CMV) assay (QuiagenTM, Courtabœuf, France).
Aim of the study
The aim of the study is to determine the extent to which the QF-CMV can be use to identify, among SOT recipients with a CMV viremia, those that may not need antiviral therapy.
Methods
Participation to the study will be proposed to SOT recipients with an asymptomatic CMV infection with a blood viral load between 1,000 and 15,000 IU/mL.
The QF-CMV will be performed in included participants, and the result will be given or not to the clinician in charge (according to the attributed group through randomisation).
In the following weeks, the viral load will be monitored, along with creatininemia, cell blood count, and kalemia (to detect antiviral adverse effect).
The participants will be sampled:
Endpoints
The primary endpoint is the rate of uncontrolled infection 5 to 12 days after QF-CMV sampling, defined as follows:
The secondary endpoint is the is the occurrence antiviral adverse effects (hematoxicity or nephrotoxicity).
Full description
Context.
Solid organ transplant (SOT) recipients are at high risk of opportunistic infections, particularly due to cytomegalovirus (CMV).
Regarding CMV infection after transplantation, two approaches are possible: either antiviral prophylaxis for several months, followed by monitoring of blood CMV viral load (or viremia), or immediate monitoring of viral load without prophylaxis.
In both cases, the detection of a CMV viral load raises a complex question: is antiviral treatment necessary? Indeed, not all viremia leads to CMV disease: some patients spontaneously control their viremia.
In order to limit unnecessary treatments, their toxicity and their cost, new tools are needed to identify people at high risk of developing a high viral load or CMV disease.
As CMV infection is mainly controlled by cellular immunity, measuring specific anti-CMV T lymphocyte immunity could be an interesting tool for identifying these at-risk individuals.
The QuantiFERON-CMV (QF-CMV) test (QuiagenTM, Courtabœuf, France) is an interferon-gamma (IFN-γ) release assay (IGRA), which measures the presence of anti-CMV T lymphocyte immunity. Results from previous retrospective studies suggest that in cases of CMV replication, it may be relevant to base the therapeutic attitude not only on the virological characteristics of this replication, but also on the existence of specific T lymphocyte immunity.
The aim of this study is therefore to prospectively assess the contribution of QF-CMV to therapeutic decisions in cases of intermediate CMV viral load (between 1,000 and 15,000 IU/mL).
Methods
SOT recipients with a detectable blood CMV viral load (CV1) between 1,000 and 15,000 IU/mL without symptoms (fever, organ damage) will be offered participation in the study within 48 hours of detection of this CMV viral load.
After inclusion, participants will be immediately sampled for QF-CMV.
They will be randomized (2:1) into 2 groups:
In the experimental group, the recommended attitude will depend on the QF-CMV result:
In the control group, the physician in charge will be advised to proceed according to the standard of care, based on current recommendations and local practices.
In both groups, as routinely done when a CMV viral load is detected in the blood, this parameter will be checked several times after the 1st detection (V0):
The primary endpoint is the rate of uncontrolled infection at 5 to 12 days after QF-CMV sampling (V2), defined as follows:
Conversely, the blood CMV viral load will be considered controlled if its value at V2 does not exceed 10,000 IU/mL [4 log] and :
In the event of controlled infection at V2, the physician in charge will be advised not to initiate antiviral treatment if this has not already been done, and to continue monitoring at V3 and V4.
The secondary endpoint is the occurrence of an iatrogenic event (hematoxicity or nephrotoxicity) related to antivirals; parameters that may reflect such toxicity (blood cell count, kalemia, creatinin) will be collected at inclusion (V1) and then at the 3 times mentioned above (V2 to V4).
Enrollment
Sex
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Volunteers
Inclusion criteria
Age ≥ 18 years.
Solid organ transplant recipient (heart, kidney, liver and lung)
Detectable CMV viral load between 1,000 and 15,000 IU/mL (including 2 borderline values):
Having signed an informed consent form.
Affiliated to a social security scheme.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
288 participants in 2 patient groups
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Central trial contact
Martine Pernollet, MD; Olivier Epaulard, MD, PhD
Data sourced from clinicaltrials.gov
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