De-novo Initiation of Letermovir vs Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Trans Recip
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Letermovir group (study group) Letermovir 480 mg once daily |
Drug: Letermovir 480 mg once daily
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.
|
| Other: Historically matched AA kidney transplant recipients who received valganciclovir Compare outcomes to a historical group of 50 AA kidney transplant recipients who have received valganciclovir prophylaxis |
Other: Historical/Control
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.
|
Outcome Measures
Primary Outcome Measures
- Incidence of cytomegalovirus viremia (defined as CMV PCR > 137 units/ml) or symptomatic disease in AA kidney transplant recipients [up to one year after transplantation]
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
Secondary Outcome Measures
- Incidence of Leukopenia (defined as WBC < 2.5 x 103 cells/mm3 beyond the first 2 weeks of transplantation, while on pharmacologic CMV prophylaxis) [From 2 weeks up to 26 weeks post-transplant]
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
- Impact of Pharmacological Prophylaxis on CMV T-Cell immunity up to 1 year post-transplant [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
- Incidence of acute kidney allograft rejection up to one year after transplantation [up to 1 Year post-transplant]
acute kidney allograft rejection up to one year after transplantation
- Impact of Pharmacologic CMV Prophylaxis on Mycophenolate dosage up to 6 months post-transplant [Up to 6 months post-transplant]
Changes in mycophenolate dosage (assessed by review of patient's chart) up to 6 months post-transplant
- Incidence of de novo donor specific antibody formation up to 1 year after transplant [up to 1 Year post-transplant]
de novo donor specific antibody formation up to one year after transplantation
- Tolerability of Letermovir in AA kidney transplant recipients up to 6 months post-transplant, using a tolerability assessment questionnaire [up to 6 months post-transplant]
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).
- Correlation between CYP3A5*1 and its impact on tacrolimus metabolism and incidence of kidney allograft rejection up to 1 year post-transplant [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
Eligibility Criteria
Criteria
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
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Male or female age ≥ 18 years old
-
African American race
-
CMV high risk (D+/R-)
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Ability to provide informed consent before any trial related activities
Exclusion Criteria
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Re-transplantation
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Panel of reactive antibody ≥80% at the time of transplant
-
Positive cytotoxic cross match at the time of transplant
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Pregnancy and Breastfeeding
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Prisoners
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Patients with hypersensitivity to acyclovir, valacyclovir or any of its components
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Patients with hypersensitivity to Letermovir or any of its components
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Virginia Commonwealth University
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Gaurav Gupta, MD, Virginia Commonwealth University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HM20027540