Clinical trial NCT02538172: Cell-mediated Immunity for Prevention of CMV Disease
Official title: Monitoring of Specific Cytomegalovirus Cell-mediated Immunity (CMV-CMI) for Optimization of Preventive Strategies Against CMV Infection in High-risk Solid-organ Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cytomegalovirus Infections
Keywords: Cell-mediated immunity
Antiviral prophylaxis
Transplantation
Lead sponsor: University of Lausanne Hospitals
Sponsor class: OTHER
First posted: 2015-09-02
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: An open-label randomized controlled trial to adapt the duration of antiviral prophylaxis in D+/R- patients and in R+ patients receiving ATG according to the result of the T-Track® CMV assay. Investigators will include kidney and liver transplant recipients. Patients will be randomized during the first month post transplant.

In the interventional arm, while the patient is on antiviral prophylaxis, CMI will be monitored every 4 weeks from the 2nd month after transplant. Measurement of CMV CMI will be done in real time by using the T-Track® CMV assay. The continuation of antiviral prophylaxis will depend on the result of the assay:

* T-Track positive (patient at lower risk): discontinuation of the antiviral drug
* T-Track negative (patient at higher risk): continuation of the antiviral drug until the maximal duration of prophylaxis (3 to 6 months) The standard arm will receive a standard fixed duration of antiviral prophylaxis (3 months for R+ thymoglobulin treated-patients and 6 months for D+/R- patients). Measurement of CMV CMI by both T-Track® CMV and the Quantiferon-CMV® assays will be done at the same time points of the interventional arm, but the result will not be known by the investigators.

After discontinuation of prophylaxis, patients in both arms will be followed for the development of CMV replication at each visit using the local PCR assay and antiviral therapy will be administered in case of CMV infection according to local guidelines.

The co-primary endpoints will be the incidence of CMV disease or antiviral-treated CMV replication during the first 12 months post transplant AND the duration of antiviral prophylaxis.


Eligibility criteria: Inclusion Criteria:

* 18 years old
* Kidney or liver transplantation
* Scheduled to receive CMV antiviral prophylaxis:
* CMV D+/R- patients
* Patients receiving lymphocyte-depleting antibodies (thymoglobulin® or ATG®)

Exclusion Criteria:

* Unable to provide informed consent
* Unable or unwilling to comply with study protocol

Primary outcomes:
measure: Incidence of CMV infection
timeFrame: one year
measure: Duration of antiviral prophylaxis
timeFrame: one year
Secondary outcomes:
measure: Graft survival
timeFrame: one year
measure: Incidence of CMV viremia using standardized measure
timeFrame: one year
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Universität Basel
city: Bern
country: Switzerland
facility: Universitätsspital Bern
city: Genève
country: Switzerland
facility: Hopitaux Universitaires de Genève
city: St. Gallen
country: Switzerland
facility: Kantonsspital St.Gallen
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
Study officials:
affiliation: University of Lausanne Hospitals
name: Oriol Manuel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Manuel O, Husain S, Kumar D, Zayas C, Mawhorter S, Levi ME, Kalpoe J, Lisboa L, Ely L, Kaul DR, Schwartz BS, Morris MI, Ison MG, Yen-Lieberman B, Sebastian A, Assi M, Humar A. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013 Mar;56(6):817-24. doi: 10.1093/cid/cis993. Epub 2012 Nov 29.
citation: Manuel O. Clinical Experience with Immune Monitoring for Cytomegalovirus in Solid-Organ Transplant Recipients. Curr Infect Dis Rep. 2013 Sep 29. doi: 10.1007/s11908-013-0369-6. Online ahead of print.
citation: Humar A, Lebranchu Y, Vincenti F, Blumberg EA, Punch JD, Limaye AP, Abramowicz D, Jardine AG, Voulgari AT, Ives J, Hauser IA, Peeters P. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant. 2010 May;10(5):1228-37. doi: 10.1111/j.1600-6143.2010.03074.x. Epub 2010 Mar 26.