Preventing CMV after receiving a CMV-positive donor kidney using daily antiviral pills or weekly blood monitoring

Kidney Transplant Preemptive Therapy or Prophylaxis (KPoP) for CMV Prevention in D+R- Recipients

This study will test whether taking daily antiviral pills for 200 days or doing weekly blood checks and treating only if the virus appears is better at preventing CMV disease in adults who get a kidney from a CMV-positive donor and are themselves CMV-negative.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Locations: 5 sites (San Francisco, California and 4 other locations)
• Trial ID: NCT06798909 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, open-label, multicenter Phase 3 trial that enrolls adult CMV-seronegative recipients of CMV-seropositive donor kidneys and randomizes them 1:1 within 7 days of transplant. One arm receives antiviral prophylaxis (valganciclovir 900 mg once daily or letermovir 480 mg once daily, dose-adjusted per FDA labeling) for 200 days post-transplant. The other arm follows a preemptive strategy with weekly central-laboratory plasma CMV PCR monitoring for 100 days and starts oral valganciclovir 900 mg twice daily (renally dosed per label) only if CMV DNAemia is detected, continuing until two consecutive weekly negatives. The trial compares the two approaches for prevention of CMV disease and related complications in this high-risk donor-positive/recipient-negative population.

Who should consider this trial

Good fit: Adults aged 18 or older who are CMV IgG negative, received a kidney from a CMV IgG positive donor within the past 7 days, provided informed consent, and meet pregnancy-testing and contraception requirements are eligible.

Not a fit: People who are CMV-seropositive, received non-kidney organs, have contraindications to the study antivirals, or cannot comply with study monitoring are unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, this approach could reduce CMV disease and related complications after high-risk kidney transplants, potentially lowering hospital stays and protecting the transplanted kidney.

How similar studies have performed: Previous randomized and observational work in solid-organ transplantation has shown that antiviral prophylaxis reduces CMV disease compared with no prophylaxis and that preemptive strategies can also be effective, while letermovir is a newer agent with stronger evidence in stem-cell transplant settings and emerging data in solid-organ transplant.

Eligibility criteria

Inclusion Criteria:

1. Subject or legally authorized representative has provided written informed consent.
2. Age ≥ 18 years of age at the time of informed consent.
3. 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.
4. Received a kidney transplant from a CMV seropositive (IgG positive) donor in the past 7 days prior to enrollment
5. 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).
6. 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:

1. In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)
2. Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant
3. Allergy to valganciclovir/ganciclovir or Letermovir
4. Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes COVID convalescent plasma)
5. 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.
6. Most recent platelet count post-transplant \<25,000/uL
7. Most recent ANC performed post-transplant \<1000/uL
8. Multi-organ transplant (except simultaneous kidney-pancreas) within the past 7 days
9. Prior or planned receipt of a hematopoietic cell transplant
10. Baseline immunodeficiency prior to transplant, including but not limited to:

    1. Known or suspected HIV infection
    2. Congenital or acquired immunodeficiency
11. Unacceptable immunosuppression

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

Where this trial is running

San Francisco, California and 4 other locations

• University of California, San Francisco School of Medicine — San Francisco, California, United States (Recruiting)
• University of Miami Miller School of Medicine — Miami, Florida, United States (Recruiting)
• Emory University School of Medicine — Atlanta, Georgia, United States (Recruiting)
• Robert Wood Johnson Health Network Barnabas Health — Livingston, New Jersey, United States (Recruiting)
• Medical College of Virginia Commonwealth — Richmond, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Abhijit P. Limaye, MD — University of California, San Francisco
• Study coordinator: Megan Gish

Conditions Cytomegalovirus; Kidney Transplant; Complications; Kidney Diseases