Comparison of Two Strategies for Monitoring HCMV Breakthrough Infections During Letermovir Prophylaxis. a Multicenter, Randomized, Open-label Trial

Status: Recruiting
Location: See all (8) locations...
Intervention Type: Diagnostic test
Study Type: Interventional
Study Phase: Not Applicable
SUMMARY

The goal of this clinical trial is to compare two strategies to monitor human cytomegalovirus (HCMV) infections in transplanted patients receiving letermovir (LTV) as anti-HCMV prophylaxis. HCMV infection after transplantation is diagnosed by detection of HCMV DNA in blood. However, due to the peculiar mechanism of action of LTV, most episodes of HCMV DNA detection are caused by release in the blood stream of non-infectious HCMV DNA. In true episodes of productive infection, HCMV DNA in blood is present inside the virion and therefore is resistant to DNAse digestion. Conversely, when non-infectious free-floating HCMV DNA is released in the bloodstream, it will be degraded after treatment of plasma with DNAse and will not be detectable by real-time PCR assays. Researchers will compare determination of HCMV DNA in blood with or without previous digestion of non-infectious free-floating DNA with DNAse. In patients of the Control group HCMV DNA will be tested without DNAse digestion. If HCMV DNA is positive, patients will stop LTV prophylaxis and receive antiviral therapy with another drug. In patients of the Study group HCMV DNA will be tested after DNAse digestion. Only if HCMV DNA is positive after DNAse digestion, patients will stop LTV prophylaxis and receive antiviral therapy with another drug. The main aim of the study is to demonstrate that, by avoiding inappropriate antiviral therapy during LTV prophylaxis, transplant patients will suffer of lower antiviral-drug-related toxicity. A monitoring strategy able to identify true episodes of HCMV productive infection during LTV prophylaxis will lead to a lower rate of inappropriate antiviral therapy and drug-related toxicity without an increased risk of HCMV disease.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Age\>18 years.

• Allogeneic hematopoietic stem cell transplant.

• HCMV IgG seropositivity before transplant

• Written informed consent.

• LTV prophylaxis administration

Locations
Other Locations
Italy
ASST-Ospedale Papa Giovanni XXIII
NOT_YET_RECRUITING
Bergamo
IRCCS Azienda Ospedaliero-Universitaria di Bologna
NOT_YET_RECRUITING
Bologna
ASST-Spedali Civili
RECRUITING
Brescia
ASST Grande Ospedale Metropolitano Niguarda
NOT_YET_RECRUITING
Milan
Fondazione IRCCS Policlinico San Matteo
RECRUITING
Pavia
Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
NOT_YET_RECRUITING
Reggio Calabria
AOU Policlinico Umberto I
NOT_YET_RECRUITING
Roma
Policlinico Universitario Agostino Gemelli
NOT_YET_RECRUITING
Roma
Contact Information
Primary
Daniele Lilleri, MD
d.lilleri@smatteo.pv.it
+39 0382 502420
Backup
Irene Cassaniti, PhD
i.cassaniti@smatteo.pv.it
+39 0382 502420
Time Frame
Start Date: 2023-01-09
Estimated Completion Date: 2026-03
Participants
Target number of participants: 140
Treatments
Experimental: Study
Patients will stop LTV shifting to GCV/VGCV/FOS pre-emptive therapy in case of positive HCMV DNA and subsequent confirmation of productive infection by detection of DNAse-resistant HCMV plasma DNAemia. However, for safety reasons, patients of the Study arm will stop LTV and shift to pre-emptive therapy in case of HCMV DNAemia \>10,000 copies/ml whole blood in two consecutive samples, even if DNAse-resistant HCMV plasma DNAemia is negative.
Active_comparator: Control
Patients will stop LTV shifting to GCV/VGCV/FOS pre-emptive therapy in case of positive HCMV DNAemia confirmed in two consecutive samples.
Sponsors
Leads: Fondazione IRCCS Policlinico San Matteo di Pavia
Collaborators: Ministero della Salute, Italy

This content was sourced from clinicaltrials.gov