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Cytomegalovirus DiseasePhase 4NCT04904614

Letermovir Use in Heart Transplant Recipients

A Phase 4 study testing Letermovir in people with Cytomegalovirus Disease and Cytomegalovirus Infections, run by Tufts Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open label trial in which letermovir will be given as prophylaxis for the prevention of cytomegalovirus (CMV) infection and disease to all heart transplants who are at risk for cytomegalovirus. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Letermovir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
5 Jan 2022to 14 Jan 2025
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults between 18-70 will be eligible for participation
  • Written informed consent and able to participate with follow up
  • Heart transplant recipients who are not Cytomegalovirus (CMV) donor negative and CMV recipient negative (CMV D-/R-)
  • Not enrolled in competing clinical trials

Who cannot join

  • Dual heart and kidney transplant recipients
  • Patients who do not survive 72 hours post transplant
  • HIV infection
  • Patients with creatinine clearance less than 10 ml per min at time of enrollment
  • Hypersensitivity to letermovir
  • On continuous veno-venous hemofiltration or renal dialysis at the time of enrollment
Show all 22Show fewer
  • Received a previous solid organ transplant or stem cell transplant.
  • Has Child Pugh Class C severe hepatic insufficiency at screening.
  • Has both moderate hepatic insufficiency AND moderate to severe renal insufficiency at screening.
  • Note: Moderate hepatic insufficiency is defined as Child Pugh Class B; moderate to severe renal insufficiency is defined as Creatine Clearance <50 mL/min, as calculated by the Cockcroft-Gault equation (as above), respectively.
  • Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy.
  • Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy.
  • Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy.
  • Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or put the participant at undue risk, as judged by the investigator, such that it is not in the best interest of the participant to participate in this study.
  • Has exclusionary laboratory value at screening, as listed in Table 1. Table 1 Laboratory Exclusion Criteria Laboratory Assessment Exclusionary Value
  • Hemoglobin <8 g/dL Platelets <25,000 cells/µL Absolute neutrophil count <1,000 cells/µL Total bilirubin >2.5 × ULN ALT >5 × ULN AST >5 × ULN
  • ALT = alanine aminotransferase; AST = aspartate aminotransferase; CMV = cytomegalovirus; IgG = immunoglobulin G; ULN = upper limit of normal
  • Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5× half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing on this study. Participants previously treated with an investigational monoclonal antibody will be eligible to participate after a 150-day washout period.
  • Note: Investigational regimens involving combinations of approved agents are not permitted. Other non-interventional or other observational studies are allowed.
  • Has previously participated in this study or any other study involving letermovir.
  • Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.
  • -

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Tufts Medical Center

    Boston, Massachusetts, 02111

Other trials in United States

About this study

Official title: Evaluation of the Tolerability and Clinical Effectiveness of Letermovir in Heart Transplantation

This is an open label trial in which letermovir will be given as prophylaxis for the prevention of cytomegalovirus (CMV) infection and disease to all heart transplants who are at risk for cytomegalovirus. The study will compare a 30 patient prospective cohort to a retrospective cohort of 374 heart transplant recipients for the rates of neutropenia. In addition, the tolerability of letermovir will be assessed in this population.

Read the detailed description

This open label trial will follow 30 heart transplant recipients at Tufts Medical Center who will receive letermovir in a dose of 480 mg daily for either 3 or 6 months depending on the CMV risk category, and who will be followed for one year. Comparison will be made to a cohort of heart transplant recipients as historical controls in a recently presented study (Chow, J, et al ISHLT 2021). Standard follow up will be provided as if the patients were receiving valganciclovir prophylaxis. Post prophylaxis T cell immunity to all subjects enrolled will be tested. Clinical outcomes are detailed below.

Being tested
Letermovir
Keywords
cytomegalovirus, letermovir, heart transplantation
Medical subject headings
Cytomegalovirus Infections, Neutropenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LetermovirDrug

    Also called Prevymis

    Open label trial of the licensed drug, letermovir, in a population of heart transplant recipients for which it is not yet licensed

Study groups in NCT04904614
Study groupRoleWhat they receive
single armOtherLetermovir 480 mg daily for cmv prophylaxis
Receives: Drug: Letermovir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Patients With Neutropenia Compared to Historical Controls

    We will count the number of patients with neutropenia seen over one year and calculate the proportion who become neutropenic. A comparison group of historic controls from a similar population is available for comparison. We know the control group has a 30% likelihood of becoming neutropenic at one year.

    Measured: 12 months

Secondary outcomes (5)

  1. Rate of CMV Infection in Letermovir Recipients Compared to Historical Controls

    Number of patients who develop CMV infection, comparison will be made to historic control group who were taking valganciclovir for CMV prophylaxis

    Measured: 1 year

  2. Rate of Opportunistic Infections in Letermovir Arm Compared to Historical Controls

    Number of patients who develop an opportunistic infection

    Measured: 1 year

  3. Tolerability and Compliance of Letermovir

    Number of patients with adverse events will be collected using a data questionnaire, and examination of lab data, need for subsequent hospitalization.

    There is no comparator group for this purely descriptive outcome.

    Measured: 1 year

  4. Use of Granulocyte Colony Stimulation Factor (GCSF) in Letermovir Recipients Compared to Historical Controls

    Comparison of Proportions

    Measured: 1 year

  5. Measure of CMV Specific T Cell Immunity in Letermovir Recipients

    Single measurement of specific T-cell immune function to CMV. There is no comparator arm for this outcome because this test did not exist at time of historical controls.

    This is a measure of CMV specific T-cell immunity based on a commercial assay that yields one of 3 results: positive (CMV T-cell function is measured), indeterminate, negative (CMV T-cell function is not measured). A positive T-cell test is considered a better outcome.

    Measured: single time point measured within 2 weeks after completion of prophylaxis therapy, at either 3 months or 6 months, depending on duration of prophylaxis

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2021
  2. Study start5 Jan 2022
  3. Primary completion14 Jan 2025
  4. Study completion14 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Model description
Open label trial
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04904614
Sponsor's protocol ID
00001538
Status last verified
Jun 2025
First submitted
10 May 2021
Last updated
29 Jul 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29596116

  • Snydman DR. Epidemiology of infections after solid-organ transplantation. Clin Infect Dis. 2001 Jul 1;33 Suppl 1:S5-8. doi: 10.1086/320897.

    PubMed 11389515

  • Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, Haider S, Ullmann AJ, Katayama Y, Brown J, Mullane KM, Boeckh M, Blumberg EA, Einsele H, Snydman DR, Kanda Y, DiNubile MJ, Teal VL, Wan H, Murata Y, Kartsonis NA, Leavitt RY, Badshah C. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017 Dec 21;377(25):2433-2444. doi: 10.1056/NEJMoa1706640. Epub 2017 Dec 6.

    PubMed 29211658

  • Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011 Oct;85(20):10884-93. doi: 10.1128/JVI.05265-11. Epub 2011 Jul 13.

    PubMed 21752907

  • Kaul DR, Stoelben S, Cober E, Ojo T, Sandusky E, Lischka P, Zimmermann H, Rubsamen-Schaeff H. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant. 2011 May;11(5):1079-84. doi: 10.1111/j.1600-6143.2011.03530.x.

    PubMed 21521474

  • Marschall M, Stamminger T, Urban A, Wildum S, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother. 2012 Feb;56(2):1135-7. doi: 10.1128/AAC.05908-11. Epub 2011 Nov 21.

    PubMed 22106211

  • Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, Ruebsamen-Schaeff H, Zimmermann H. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010 Mar;54(3):1290-7. doi: 10.1128/AAC.01596-09. Epub 2010 Jan 4.

    PubMed 20047911

  • Giulieri S, Manuel O. QuantiFERON(R)-CMV assay for the assessment of cytomegalovirus cell-mediated immunity. Expert Rev Mol Diagn. 2011 Jan;11(1):17-25. doi: 10.1586/erm.10.109.

    PubMed 21171917

  • Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD; Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87-91. doi: 10.1093/cid/ciw668. Epub 2016 Sep 28.

    PubMed 27682069

  • Gardiner BJ, Nierenberg NE, Chow JK, Ruthazer R, Kent DM, Snydman DR. Absolute Lymphocyte Count: A Predictor of Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients. Clin Infect Dis. 2018 Oct 15;67(9):1395-1402. doi: 10.1093/cid/ciy295.

    PubMed 29635432

  • Arbo MD, Snydman DR. Influence of blood culture results on antibiotic choice in the treatment of bacteremia. Arch Intern Med. 1994 Dec 12-26;154(23):2641-5. doi: 10.1001/archinte.1994.00420230024004.

    PubMed 7993147

  • George MJ, Snydman DR, Werner BG, Griffith J, Falagas ME, Dougherty NN, Rubin RH. The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med. 1997 Aug;103(2):106-13. doi: 10.1016/s0002-9343(97)80021-6.

    PubMed 9274893

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Letermovir in people with Cytomegalovirus Disease and Cytomegalovirus Infections, run by Tufts Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients With Neutropenia Compared to Historical Controls (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04904614, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.

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