Cytomegalovirus Infections, Kidney Transplant Infection, Pancreas Transplant
Conditions
Brief summary
This study is designed to assess how effective letermovir is in preventing recurrence of cytomegalovirus (CMV) infection in adult kidney or kidney/pancreas transplant recipients who are UW Health patients. Participants will be in the study for about 6 months.
Detailed description
Study Population: Patients over 18 years of age who have undergone kidney or simultaneous kidney/pancreas transplant and are high-risk CMV serostatus (D+/R-) at time of transplant who develop CMV viremia that necessitates treatment per our institutional protocol (enrolled in our CMV stewardship monitoring initiative) and demonstrate proven or presumptive lack of cell-mediated immunity, either by CMI testing or risk factor screening. Patients will be converted from treatment with ganciclovir derivatives to letermovir (480 mg tablet taken orally once daily) when the viral load via standard of care (SOC) weekly monitoring is \< 500 IU/mL. This differs from SOC which only allows conversion to secondary prophylactic treatment after CMV is no longer detected on polymerase chain reaction (PCR) for 2 consecutive weeks. Thus, liberalization of conversion threshold will allow for reduced exposure to valganciclovir via reduced duration of therapy allowing relief of the myelosuppressive toxicity and creates an environment conducive to cell-mediated immunity (CMI). The primary objective is to assess the efficacy of letermovir as secondary prophylaxis after treatment of CMV infection. The secondary objective is to detect the development of cytomegalovirus-specific cell-mediated immunity as determined by a positive result using the Eurofins-Viracor CMV inSIGHTTM T Cell Immunity Testing per manufacturer specifications.
Interventions
DRUGLetermovir
480 mg taken orally once daily, for 84 days
Sponsors
University of Wisconsin, Madison
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* undergone kidney or simultaneous kidney/pancreas transplant * high-risk CMV serostatus (D+/R-) at time of transplant * develop CMV viremia that necessitates treatment per our institutional protocol (enrolled in the CMV stewardship monitoring initiative) * demonstrate proven or presumptive lack of CMI, either by CMI testing or risk factor screening * able to provide informed consent to participate
Exclusion criteria
* contraindication to letermovir or its excipients * develop ganciclovir-resistant CMV infection * currently participating in any study involving the administration of a CMV vaccine or another CMV investigational agent * unable or unwilling, in the opinion of the Investigator, to comply with the protocol * pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of distinct episodes of any cytomegalovirus replication greater than 1000 IU/mL | up to 90 days after withdrawal of secondary prophylaxis (up to 6 months on study) | To test the hypothesis that letermovir will be associated with reduced incidence of recurrent viremia, recurrence will be measured defined as incidence of any cytomegalovirus replication greater than 1000 IU/mL requiring treatment after withdrawal of secondary prophylaxis. |
| Duration of valganciclovir (VGC) Treatment | up to 2 months | To test the hypothesis that letermovir will be associated with reduced duration of (val)ganciclovir treatment, the duration of VGC treatment will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Positive Result for T-Cell Immunity Panel (TCIP) Testing | letermovir initiation (Day 0), at secondary prophylaxis completion (Week 12 +/- 28 days) | To test the hypothesis that letermovir will be associated with increased development of cytomegalovirus-specific cell-mediated immunity when compared to a literature-based control, development of cytomegalovirus-specific cell-mediated immunity as determined by a positive result using the Eurofins-Viracor CMV inSIGHTTM T-Cell Immunity Testing per manufacturer specifications will be measured. TCIP will be collected from the medical record at these timepoints if possible. Given SOC, access to this test is not always available to all patients at both timepoints. |
Countries
United States
Contacts
CONTACTSandesh Parajuli, MBBS
PRINCIPAL_INVESTIGATORSandesh Parajuli, MBBS
University of Wisconsin, Madison
Outcome results
None listed