Letermovir vs Valganciclovir in CMV R+ Kidney Transplant

May 6, 2026 updated by: Elisabeth Kincaide

Letermovir Versus Valganciclovir for 90 Days in CMV Seropositive Kidney Transplant Recipients: Results of a Single-center Experience.

The purpose of this study is to find out whether letermovir can help prevent cytomegalovirus (CMV) infection in kidney transplant recipients who are CMV seropositive. To do this, researchers will compare patients who received letermovir with a group of historical patients who received valganciclovir ("mini dose"). Both groups will be on CMV prophylaxis drug for 90 days post-transplant.

The main question the study wants to answer is:

• Does letermovir work as well as valganciclovir in preventing CMV infections during the first 12 months after a kidney transplant?

The study will also look at other important questions:

  • Is letermovir easier for patients to tolerate than valganciclovir?
  • How long does it take for a CMV infection to appear in each group?
  • Are there differences in "breakthrough" CMV infections between the two medications?
  • For patients who develop CMV that becomes resistant to treatment, are the resistance patterns different between the two groups

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to evaluate the efficacy and tolerability of letermovir compared to standard-of-care, valganciclovir, for the prevention of clinically significant cytomegalovirus (CMV) infection in CMV moderate risk adult kidney transplant recipients.

A 3:1 match of historical valganciclvoir:letermovir arm

• Matching criteria:

  • Induction agent: lymphocyte-depleting (rabbit anti-thymocyte globulin or alemtuzumab) versus non-lymphocyte depleting (basiliximab)
  • Delayed graft function (dialysis within one week of kidney transplant)
  • MMF dose at de novo discharge (weight-based vs non-weight based)

Study Arms:

  • Letermovir Arm:

    • Letermovir 480 mg PO daily starting POD 4 through 10 OR
    • Letermovir 240 mg PO daily if given concomitantly with cyclosporine, for 90 days
    • Will be given with acyclovir 400 mg PO BID (or 200 PO BID if CrCl <25) for 90 days

  • Historical Arm:

    • Valganciclovir 450 mg PO daily (adjusted for renal function) for 90 days

      • CrCl 25-30: valganciclovir 450 mg PO q 48 h
      • CrCl <25: Valganciclovir 450 mg PO three times weekly

Outcomes:

  • Primary Efficacy Objective:

    • Incidence of patients with clinically significant CMV infection at 12 months post kidney transplant in patients who received letermovir versus standard of care valganciclovir

      • Clinically Significant CMV Infection: CMV disease or symptomatic viremia requiring therapeutic intervention

  • Secondary Objectives:

    • Tolerability:

      • Proportion of patients with leukopenia or neutropenia (composite) in patients who received letermovir versus standard of care valganciclovir
  • Leukopenia: white blood cells < 3500 cells/uL

  • Neutropenia: absolute neutrophil count < 1000 cells/uL

    • Intolerability or early drug discontinuation

  • Proportion of patients who discontinue the study drug prematurely due to adverse events or intolerance

    o Efficacy:

    • Time-to clinically significant CMV infection (days)
    • Breakthrough CMV while on CMV prophylaxis

  • CMV Viremia

    • Detection of CMV DNA in blood via PCR

  • Clinically significant CMV infection

    • CMV resistance
  • Detection of CMV strains with genotypic or phenotypic resistance to antiviral agents used in prophylaxis or treatment

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (both arms):

  • ≥18 years old
  • Kidney transplant recipient with documented CMV IgG seropositive status (R+) within 90 days prior to transplant

Inclusion Criteria (letermovir arm):

  • Males agree to use contraception and refraining from donating sperm for 290 days post-treatment initiation
  • Females of child-bearing potential agree to follow contraception guidance for 290 days post-treatment initiation

Exclusion Criteria (both arms):

  • Multiorgan organ transplant
  • Received previous solid organ transplant or HSCT
  • Unable to take oral medications
  • Uncontrolled infections at the time of enrollment
  • Hemodynamically unstable or on mechanical ventilation at the time of enrollment
  • Documented HBsAg or detectable HCV RNA 90 days prior to enrollment or HCV+ donor
  • Pregnant or breastfeeding or planning to be pregnant, breastfeeding or donating eggs during study period and 90 days post cessation
  • Received any anti-CMV drug treatment within 7 days prior to enrollment
  • Current user of recreational or illicit drugs or alcohol dependence
  • History of CMV disease prior to enrollment

Exclusion Criteria (letermovir arm):

  • Previously participated in a letermovir study or any other study with CMV investigational agents
  • On dialysis or plasmapheresis at the time of enrollment
  • Known or suspected hypersensitivity to active or inactive ingredients from letermovir or acyclovir formulations
  • Child-Pugh Class C severe hepatic insufficiency
  • Currently participating or has participated in a study with an unapproved compound of device within 28 days or 5 half-lives of this study
  • Contraindications per letermovir or acyclovir package insert: patients on pimozide, ergot alkaloids; or pitavastatin and simvastatin when co-administered with cyclosporine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Letermovir
Prospective letermovir prophylaxis
Drug: Letermovir
Letermovir 480 mg PO daily or 240 mg PO daily (if on cyclosporine) for 90 days post kidney transplant
Other: Valganciclovir
Historical valganciclovir prophylaxis
Drug: Valganciclovir CMV Prophylaxis
Valganciclovir 450 mg PO daily for 90 days post kidney transplant (Historical Control)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CMV Infection
Time Frame: 12 months post kidney transplant
Incidence of patients with clinically significant CMV infection at 12 months post kidney transplant in patients who received letermovir versus standard of care valganciclovir.
12 months post kidney transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Elisabeth Kincaide

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

April 29, 2026

First Submitted That Met QC Criteria

April 29, 2026

First Posted (Actual)

May 6, 2026

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00000831

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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