CMV, CMV Disease, CMV Infection, CMV Viremia
Conditions
Keywords
CMV, Kidney Transplant, Letermovir, Moderate Risk, CMV Prophylaxis, Valganciclovir, Neutropenia
Brief summary
The purpose of this study is to find out whether letermovir can help prevent cytomegalovirus (CMV) infection in kidney transplant recipients who are CMV seropositive. To do this, researchers will compare patients who received letermovir with a group of historical patients who received valganciclovir ("mini dose"). Both groups will be on CMV prophylaxis drug for 90 days post-transplant. The main question the study wants to answer is: • Does letermovir work as well as valganciclovir in preventing CMV infections during the first 12 months after a kidney transplant? The study will also look at other important questions: * Is letermovir easier for patients to tolerate than valganciclovir? * How long does it take for a CMV infection to appear in each group? * Are there differences in "breakthrough" CMV infections between the two medications? * For patients who develop CMV that becomes resistant to treatment, are the resistance patterns different between the two groups
Detailed description
The purpose of this study is to evaluate the efficacy and tolerability of letermovir compared to standard-of-care, valganciclovir, for the prevention of clinically significant cytomegalovirus (CMV) infection in CMV moderate risk adult kidney transplant recipients. A 3:1 match of historical valganciclvoir:letermovir arm • Matching criteria: * Induction agent: lymphocyte-depleting (rabbit anti-thymocyte globulin or alemtuzumab) versus non-lymphocyte depleting (basiliximab) * Delayed graft function (dialysis within one week of kidney transplant) * MMF dose at de novo discharge (weight-based vs non-weight based) Study Arms: * Letermovir Arm: * Letermovir 480 mg PO daily starting POD 4 through 10 OR * Letermovir 240 mg PO daily if given concomitantly with cyclosporine, for 90 days * Will be given with acyclovir 400 mg PO BID (or 200 PO BID if CrCl \<25) for 90 days * Historical Arm: * Valganciclovir 450 mg PO daily (adjusted for renal function) for 90 days * CrCl 25-30: valganciclovir 450 mg PO q 48 h * CrCl \<25: Valganciclovir 450 mg PO three times weekly Outcomes: * Primary Efficacy Objective: * Incidence of patients with clinically significant CMV infection at 12 months post kidney transplant in patients who received letermovir versus standard of care valganciclovir * Clinically Significant CMV Infection: CMV disease or symptomatic viremia requiring therapeutic intervention * Secondary Objectives: * Tolerability: * Proportion of patients with leukopenia or neutropenia (composite) in patients who received letermovir versus standard of care valganciclovir * Leukopenia: white blood cells \< 3500 cells/uL * Neutropenia: absolute neutrophil count \< 1000 cells/uL * Intolerability or early drug discontinuation * Proportion of patients who discontinue the study drug prematurely due to adverse events or intolerance o Efficacy: * Time-to clinically significant CMV infection (days) * Breakthrough CMV while on CMV prophylaxis * CMV Viremia * Detection of CMV DNA in blood via PCR * Clinically significant CMV infection * CMV resistance * Detection of CMV strains with genotypic or phenotypic resistance to antiviral agents used in prophylaxis or treatment
Interventions
DRUGLetermovir
Letermovir 480 mg PO daily or 240 mg PO daily (if on cyclosporine) for 90 days post kidney transplant
Valganciclovir 450 mg PO daily for 90 days post kidney transplant (Historical Control)
Sponsors
Elisabeth Kincaide
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Intervention arm with Letermovir compared to historical arm receiving Valganciclovir
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(both arms): * ≥18 years old * Kidney transplant recipient with documented CMV IgG seropositive status (R+) within 90 days prior to transplant Inclusion Criteria (letermovir arm): * Males agree to use contraception and refraining from donating sperm for 290 days post-treatment initiation * Females of child-bearing potential agree to follow contraception guidance for 290 days post-treatment initiation
Exclusion criteria
(both arms): * Multiorgan organ transplant * Received previous solid organ transplant or HSCT * Unable to take oral medications * Uncontrolled infections at the time of enrollment * Hemodynamically unstable or on mechanical ventilation at the time of enrollment * Documented HBsAg or detectable HCV RNA 90 days prior to enrollment or HCV+ donor * Pregnant or breastfeeding or planning to be pregnant, breastfeeding or donating eggs during study period and 90 days post cessation * Received any anti-CMV drug treatment within 7 days prior to enrollment * Current user of recreational or illicit drugs or alcohol dependence * History of CMV disease prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CMV Infection | 12 months post kidney transplant | Incidence of patients with clinically significant CMV infection at 12 months post kidney transplant in patients who received letermovir versus standard of care valganciclovir. |
Countries
United States
Contacts
CONTACTElisabeth Kincaide, PharmD
CONTACTSean Moore, BSN, RN
Outcome results
None listed