Kidney Transplant Preemptive Therapy or Prophylaxis for CMV Prevention in D+R Recipients

Inclusion criteria

• Subject or legally authorized representative has provided written informed consent.
• Age ≥ 18 years of age at the time of informed consent.
• Negative for IgG antibody to CMV as assessed in a CLIA-certified laboratory between 28 days prior to transplant and up to 7 days post-transplant but prior to randomization.
• Received a kidney transplant from a CMV seropositive (IgG positive) donor in the past 7 days prior to enrollment
• Individuals of reproductive (childbearing) potential must have a negative pregnancy test (serum or urine) collected prior to randomization (SOC results within 7 days prior to transplant may be used), and must also agree to use a medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence from the time of enrollment through until discontinuation of ganciclovir or valganciclovir in either arm during the intervention period.

NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy).

• If male, must agree to practice a barrier method of contraception or abstinence from the time of enrollment through 3 months after discontinuation of ganciclovir or valganciclovir in either arm during the intervention period.

Exclusion criteria

• In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)
• Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant
• Allergy to valganciclovir/ganciclovir or Letermovir
• Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes COVID convalescent plasma)
• Currently enrolled or anticipated enrollment in another interventional study that, in the opinion of scientific leadership team, could affect evaluation of the primary safety and/or efficacy outcomes.
• Most recent platelet count post-transplant <25,000/uL
• Most recent ANC performed post-transplant <1000/uL
• Multi-organ transplant (except simultaneous kidney-pancreas) within the past 7 days
• Prior or planned receipt of a hematopoietic cell transplant
• Baseline immunodeficiency prior to transplant, including but not limited to:

• Known or suspected HIV infection
• Congenital or acquired immunodeficiency
• Unacceptable immunosuppression

• Receipt of desensitization therapy prior to kidney transplant, or
• Receipt of an ABO-incompatible kidney transplant except A2 to blood type B