Kidney Transplant Preemptive Therapy or Prophylaxis for CMV Prevention in D+R Recipients
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, San Francisco
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
Valganciclovir (Pre-emptive CMV Therapy)
DrugValganciclovir, 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.
Valganciclovir CMV Prophylaxis
DrugValganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 200 days post transplantation as prophylaxis.
Treatment groups
360 Participants
are divided into 2 treatment groupsGroup A: Pre-emptive TherapyExperimental treatment 1 intervention
Group B: ProphylaxisActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of endpoint committee (EC)-confirmed CMV disease (either syndrome or end-organ) by 1-year post-transplant.
Time frame
Within 1-year post-transplantSecondary outcomes
1
Non-inferiority of PET (within a 10% margin) vs AP for EC-confirmed CMV disease by 1-year post-transplant, contingent on failure to meet the primary superiority endpoint.
Although the study sample size is powered to detect the superiority of one preventive strategy compared to the other, it is possible that the two approaches may have similar efficacy with respect to prevention of CMV disease. Therefore, should there be insufficient evidence to conclude superiority of one of the approaches, a key Secondary Outcome is a non-inferiority assessment of preemptive therapy to prophylaxis, assuming a non-inferiority margin of 10%. This margin is based on what is known about the effectiveness of the two approaches as published in literature and the potential that the two strategies could be similarly efficacious in preventing CMV disease. The success rate for the prophylaxis group is estimated to be \~80% based on a systematic review and meta-analysis with hypothesized success rates for the preemptive group expected to be higher.
Time frame
by 1-year post-transplant2
Proportion of participants with investigator-determined CMV disease
Time frame
by 1-year post transplant3
Time in days to biopsy-proven acute rejection (BIPAR)
Time frame
From date of randomization until the date of BIPAR from any cause, assessed up to 5.5 years4
Time in days to graft loss
Time frame
From date of randomization until the date of graft loss from any cause, assessed up to 5.5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of California, San Francisco
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
Source ClinicalTrials.gov