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

NCT ID: NCT06798909

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-22
• Study Completion Date: 2031-06-30

Brief Summary

This is a prospective, randomized multicenter trial of preemptive therapy (PET) vs. antiviral prophylaxis (AP) for prevention of cytomegalovirus (CMV) disease in adult D+R- kidney transplant recipients (KTR). Patients meeting study eligibility criteria and who have provided informed consent will be randomized (1:1) within 7 days of transplant to receive, in an open label design, either AP with valganciclovir 900 mg orally once daily or letermovir 480 mg orally once daily [both dose adjusted per Food and Drug Administration (FDA) label] for 200 days post-transplant), or PET (central lab weekly plasma polymerase chain reaction (PCR) monitoring for CMV deoxyribonucleic acidemia (DNAemia)) for 100 days post-transplant, with oral valganciclovir 900mg orally twice daily (or renally dosed per FDA label) at onset of CMV DNAemia at any level and continued until plasma CMV DNAemia is negative or below the level of quantitation in two consecutive weekly plasma samples. Study participants will be followed for pre-specified outcomes (clinical, laboratory, immunologic, safety) until withdrawal, death, or study closure, up to a maximum of 5.5 years post-transplant. Approximately 360 participants (180 participants in each group) will be randomized into the study.

Estimated Time to Complete Enrollment: 4 years

Conditions

Cytomegalovirus (CMV); Kidney Transplant; Complications; Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Pre-emptive Therapy

900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.

Group Type: EXPERIMENTAL

Valganciclovir (Pre-emptive CMV Therapy)

Intervention Type: DRUG

Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.

Prophylaxis

900 mg of Valganciclovir given orally once daily to subjects for 200 days post transplantation. All dosages adjusted for renal dysfunction.

Group Type: ACTIVE_COMPARATOR

Valganciclovir CMV Prophylaxis

Intervention Type: DRUG

Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 200 days post transplantation as prophylaxis.

Interventions

Valganciclovir (Pre-emptive CMV Therapy)

Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.

Intervention Type: DRUG

Valganciclovir CMV Prophylaxis

Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 200 days post transplantation as prophylaxis.

Intervention Type: DRUG

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 antibody to CMV as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory between 28 days prior to transplant and 7 days post-transplant, but prior to enrollment, and no history of positive CMV serology Immunoglobulin G (IgG) antibody

4. Received a first kidney transplant from a CMV seropositive 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 (standard of care (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 1 month after discontinuation of either PET or AP.

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, and not surgically sterile, must agree to practice barrier method of contraception or abstinence from the time of enrollment through 1 month after discontinuation of either PET or AP.

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 in another interventional study that, in the investigator's opinion, could affect evaluation of the 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 or have undergone prior organ transplant

9. Baseline immunodeficiency prior to transplant:

1. Known or suspected human immunodeficiency virus (HIV) infection

2. Congenital or acquired immunodeficiency

10. Unacceptable immunosuppression

1. Receipt of desensitization therapy prior to kidney transplant, or

2. Receipt of a blood type A, B, or O-incompatible kidney transplant, or

3. Receipt or planned receipt of any of the following: belatacept, alemtuzumab, or rituximab

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abhijit P. Limaye, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco School of Medicine

San Francisco, California, United States

Site Status: RECRUITING

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status: RECRUITING

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status: RECRUITING

Robert Wood Johnson Health Network Barnabas Health

Livingston, New Jersey, United States

Site Status: RECRUITING

Medical College of Virginia Commonwealth

Richmond, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Megan Gish

Role: CONTACT

megan.gish@ucsf.edu

415-476-1985

Facility Contacts

Puneet Sood, MD, MPH

Role: primary

puneet.sood@ucsf.edu

415-353-1551

Yoichiro Natori, MD

Role: primary

yxn138@med.miami.edu

305-355-5418

Aneesh Mehta, MD

Role: primary

aneesh.mehta@emory.edu

404-727-8435

Francis Weng, MD

Role: primary

francis.weng@rwjbh.org

973-322-5065

Guarav Gupta, MD

Role: primary

gaurav.gupta@vcuhealth.org

804-828-4104

References

Limaye AP, Budde K, Humar A, Vincenti F, Kuypers DRJ, Carroll RP, Stauffer N, Murata Y, Strizki JM, Teal VL, Gilbert CL, Haber BA. Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA. 2023 Jul 3;330(1):33-42. doi: 10.1001/jama.2023.9106.

Reference Type: BACKGROUND

PMID: 37279999 (View on PubMed)

Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.

Reference Type: BACKGROUND

PMID: 29596116 (View on PubMed)

Other Identifiers

1R01AI184205-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00020695

Identifier Type: -

Identifier Source: org_study_id