De-novo Initiation of Letermovir vs Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Trans Recip

Study Overview
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Brief Summary
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CMV viremia will be treated with either oral valganciclovir, intravenous ganciclovir or alternative agents, according to AST ID COP (American Society of Transplantation Infectious disease community of practice) guidelines.

Detailed Description
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Intervention: Letermovir prophylaxis. Prophylaxis is once daily dose of Letermovier starting Day 1 of post-transplant up until 6 months post-transplant. Participants enrolled in this study will also receive prophylactic acyclovir 400mg twice daily for the duration of their Letermovir treatment. Strategy for CMV Viremia: CMV viremia will be treated with either oral valganciclovir, intravenous ganciclovir or alternative agents, according to AST ID COP (American Society of Transplantation Infectious disease community of practice) guidelines.

Official Title
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Historical Controlled, Single Center Open Label Pilot Comparing the Effectiveness and Tolerability of De-novo Initiation of Letermovir Versus Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Transplant Recipients

Conditions
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Kidney Transplant; Complications, CMV

Intervention / Treatment
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* Drug: Letermovir 480 mg once daily
* Other: Historical/Control


Participation Criteria
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Eligibility Criteria
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Historical Control group: Inclusion Criteria Kidney transplant recipients Male or female age ≥ 18 years old African American race CMV high risk (D+/R-) received valganciclovir for CMV prophylaxis Historical Control group: Exclusion Re-transplantation Panel of reactive antibody ≥80% at the time of transplant Positive cytotoxic cross match at the time of transplant Experimental Group Inclusion Criteria Kidney transplant recipients Male or female age ≥ 18 years old African American race CMV high risk (D+/R-) Ability to provide informed consent before any trial related activities Exclusion Criteria Re-transplantation Panel of reactive antibody ≥80% at the time of transplant Positive cytotoxic cross match at the time of transplant Pregnancy and Breastfeeding Prisoners Patients with hypersensitivity to acyclovir, valacyclovir or any of its components Patients with hypersensitivity to Letermovir or any of its components If Patients are taking any of these medications: pimozide, ergot alkaloids (ergotamine, dihydroergotamine), or pitavastatin/simvastatin co-administered with cyclosporine, we will work with the prescribing physician to find an appropriate replacement therapy which will not interfere with any study-related interventions. Otherwise, participants will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Interventional, Historical Controlled, Single Center Open Label Pilot Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letermovir group (study group)<br>Letermovir 480 mg once daily | Drug: Letermovir 480 mg once daily<br>* We will test the study hypothesis in a single center, matched (1:1 fashion) pilot study of Letermovir 480 mg once daily versus historically matched AA kidney transplant recipients who received valganciclovir. We will enroll 50 AA patients over a 12-month period into the Letermovir group and compare outcomes to a historical group of 50 AA kidney transplant recipients who have received valganciclovir prophylaxis (1:1 fashion), for a total of 100 patients. We will attempt to match patients on Letermovir to the historical patients who received valganciclovir, based on age, kidney Donor profile index and the presence of panel of reactive antibodies.<br>|
| Other: Historically matched AA kidney transplant recipients who received valganciclovir<br>Compare outcomes to a historical group of 50 AA kidney transplant recipients who have received valganciclovir prophylaxis | Other: Historical/Control<br>* The control study group will include high-risk African American kidney transplant recipients cared for with Valganciclovir in the 5 years prior to the enrollment start for the study group. This time frame is based upon the current volume of transplants done at VCU. On average 30 liver and/or kidney transplants are done per month. Thus, 5 years should be an adequate time frame to mine enough number of participants to answer our primary research hypothesis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of cytomegalovirus viremia (defined as CMV PCR > 137 units/ml) or symptomatic disease in AA kidney transplant recipients | The incidence of cytomegalovirus viremia (defined as CMV PCR > 137 units/ml) or symptomatic disease in AA kidney transplant recipients by one year post-transplantation | up to one year after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Leukopenia (defined as WBC < 2.5 x 103 cells/mm3 beyond the first 2 weeks of transplantation, while on pharmacologic CMV prophylaxis) | The incidence of leukopenia (defined as WBC < 2.5 x 103 cells/mm3 beyond the first 2 weeks of transplantation, while on pharmacologic CMV prophylaxis)- assessed from 2 weeks up to 26weeks post-transplant | From 2 weeks up to 26 weeks post-transplant | 
| Impact of Pharmacological Prophylaxis on CMV T-Cell immunity up to 1 year post-transplant | CMV T-cell immunity assay, assessed up to 1 year post-transplant. At 12, 26 and 52 weeks post-transplant | up to 1 Year post-transplant | 
| Incidence of acute kidney allograft rejection up to one year after transplantation | acute kidney allograft rejection up to one year after transplantation | up to 1 Year post-transplant | 
| Impact of Pharmacologic CMV Prophylaxis on Mycophenolate dosage up to 6 months post-transplant | Changes in mycophenolate dosage (assessed by review of patient's chart) up to 6 months post-transplant | Up to 6 months post-transplant | 
| Incidence of de novo donor specific antibody formation up to 1 year after transplant | de novo donor specific antibody formation up to one year after transplantation | up to 1 Year post-transplant | 
| Tolerability of Letermovir in AA kidney transplant recipients up to 6 months post-transplant, using a tolerability assessment questionnaire | Tolerability of Letermovir in AA kidney transplant recipient up to 6 months post-transplant (assessed through patient observation, tolerability assessment questionnaire, obtaining medical history and conduction physical examination during visits, receiving an unsolicited complaint from the participant, and an abnormal value or result from a clinical or laboratory evaluation). | up to 6 months post-transplant | 
| Correlation between CYP3A5*1 and its impact on tacrolimus metabolism and incidence of kidney allograft rejection up to 1 year post-transplant | correlation between CYP3A5*1 and tacrolimus metabolism and incidence of kidney allograft rejection up to one year after transplantation | up to 1 Year post-transplant |