Evaluation of the Prophylactic Use of Letermovir in Kidney Transplant Recipients at Risk of Cytomegalovirus Infection

NCT06341686 | Not Yet Recruiting Phase 3

• 1 other identifier: 75471023.2.0000.0082
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The two main cytomegalovirus (CMV) prevention strategies are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT), but is associated with high rates of neutropenia and late onset of post-prophylactic disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients, but is rarely used after solid organ transplant recipients due to logistical considerations.

Conditions

CMV Infection

Keywords

Cytomegalovirus; Letermovir; Kidney transplant

Outcome Measures

Primary Outcomes (1)

• Incidence of CMV syndrome or disease

  Proportion (%) of CMV syndrome or disease

  6 months after transplantation

Secondary Outcomes (2)

• Incidence of patients with plasma CMV DNAemia > 200 IU

  3 months

• Incidence of patients with CMV infection/syndrome/disease

  84 Days

Study Arms (2)

Letermovir

EXPERIMENTAL

Patients randomized to the prophylaxis group: Letermovir 480mg, 1x/day, from D14 to D98. Letermovir prophylaxis will start on day 14 after kidney transplantation. In both groups, CMV DNAemia will be monitored weekly until day 98 (21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 and 98), and after any acute rejection treatment occurring between 3 months and 6 months after kidney transplantation.

Drug: Letermovir 480 MG

Preemptive therapy

ACTIVE COMPARATOR

Patients randomized to the preemptive treatment group: Preemptive treatment (PET) will begin on day 21, assessing CMV DNAnemia weekly until day 98 (21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 e 98). The threshold for starting treatment with Ganciclovir is a CMV DNAemia \> 5,000 IU in a single measurement (CMV infection). measurement (CMV infection) OR any CMV DNAemia with any signs or symptoms associated with CMV (syndrome or disease).c. In both groups, CMV DNAemia will be monitored weekly until day 98 (21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 and 98), and after any acute rejection treatment occurring between 3 months and 6 months after kidney transplantation.

Drug: Ganciclovir

Interventions

Letermovir 480 MG DRUG

Oral Letermovir for 84 days is effective in the prophylaxis of CMV infection in high-risk kidney transplant recipients. Oral Letermovir for 84 days, is associated with a lower incidence of CMV infection in high-risk high-risk kidney transplant recipients. In addition, the use of Letermovir is safe and associated with a low incidence of CMV syndrome or disease up to 6 months after after kidney transplantation. Finally, prophylaxis with Letermovir is associated with a lower incidence of discontinuation of immunosuppressive drugs, reducing the risk of of clinical and subclinical acute rejection

Letermovir

Ganciclovir DRUG

The threshold for starting treatment with Ganciclovir is a CMV DNAemia \> 5,000 IU in a single measurement (CMV infection) measurement (CMV infection) OR any CMV DNAemia with any signs or symptoms associated with CMV (syndrome or disease).

Preemptive therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Kidney transplant or re-transplant recipients, aged ≥18 years;
• Undergoing induction therapy with anti-thymocyte globulin;
• Receiving maintenance treatment with Tacrolimus, Mycophenolate and Prednisone;
• Positive CMV serology for donor and recipient.

You may not qualify if:

• CMV serology positive for donor and negative for recipient;
• Multiple organ recipients, or other organs

Sponsors & Collaborators

• Hospital do Rim e Hipertensão: lead

Related Publications (8)

• 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.

  PMID: 29596116 BACKGROUND

• Henrique Pinto C, Tedesco-Silva H Jr, Rosso Felipe C, Nicolau Ferreira A, Cristelli M, Almeida Viana L, Aguiar W, Medina-Pestana J. Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation. Braz J Infect Dis. 2016 Nov-Dec;20(6):576-584. doi: 10.1016/j.bjid.2016.08.007. Epub 2016 Sep 25.

  PMID: 27643978 BACKGROUND

• de Paula MI, Bae S, Shaffer AA, Garonzik-Wang J, Felipe CR, Cristelli MP, Waldram MM, Massie AB, Medina-Pestana J, Segev DL, Tedesco-Silva H. The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis. Transplantation. 2020 Oct;104(10):2139-2147. doi: 10.1097/TP.0000000000003124.

  PMID: 31978003 RESULT

• Felipe C, Ferreira AN, de Paula M, Viana L, Cristelli M, Medina Pestana J, Tedesco-Silva H. Incidence and risk factors associated with cytomegalovirus infection after the treatment of acute rejection during the first year in kidney transplant recipients receiving preemptive therapy. Transpl Infect Dis. 2019 Dec;21(6):e13106. doi: 10.1111/tid.13106. Epub 2019 Oct 29.

  PMID: 31081566 RESULT

• Felipe CR, Ferreira AN, Bessa A, Abait T, Ruppel P, Paula MI, Hiramoto L, Viana L, Martins S, Cristelli M, Aguiar W, Mansur J, Basso G, Silva Junior HT, Pestana JM. The current burden of cytomegalovirus infection in kidney transplant recipients receiving no pharmacological prophylaxis. J Bras Nefrol. 2017 Oct-Dec;39(4):413-423. doi: 10.5935/0101-2800.20170074. English, Portuguese.

  PMID: 29319768 RESULT

• Haidar G, Boeckh M, Singh N. Cytomegalovirus Infection in Solid Organ and Hematopoietic Cell Transplantation: State of the Evidence. J Infect Dis. 2020 Mar 5;221(Suppl 1):S23-S31. doi: 10.1093/infdis/jiz454.

  PMID: 32134486 RESULT

• 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.

  PMID: 27682069 RESULT

• Chemaly RF, Chou S, Einsele H, Griffiths P, Avery R, Razonable RR, Mullane KM, Kotton C, Lundgren J, Komatsu TE, Lischka P, Josephson F, Douglas CM, Umeh O, Miller V, Ljungman P; Resistant Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials. Clin Infect Dis. 2019 Apr 8;68(8):1420-1426. doi: 10.1093/cid/ciy696.

  PMID: 30137245 RESULT

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

letermovir; Ganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Helio Tedesco

  Doctor of Renal Transplant Unit

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hélio Tedesco

CONTACT

+55 11 5087 8113; heliotedesco@medfarm.com.br

Mônica Nakamura

CONTACT

+55 11 5087 8318; Monica.nakamura@hrim.com.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigador Principal

Model Details: 1. Patients randomized to the prophylaxis group: Letermovir 480mg, 1x/day, from D14 to D98. Letermovir prophylaxis will start on day 14 after the kidney transplant. 2. Patients randomized to the preemptive treatment group: Preemptive treatment (PET) will begin on day 21, evaluating CMV DNAnemia weekly until D98.CMV DNAnemia weekly until day 98 (21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 and 98). The threshold for starting treatment with Ganciclovir is a CMV DNAemiaDNAemia \> 5,000 IU in a single measurement (CMV infection) OR any CMV DNAemia with any signs or symptoms associated with CMV (CMV syndrome or disease). 3. In both groups, CMV DNAemia will be monitored weekly until day 98 (21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 and 98), and after any acute rejection treatment occurring between 3 months and 6 months after kidney transplantation.

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: April 2, 2024
• Study Start: May 5, 2024
• Primary Completion: March 1, 2025
• Study Completion: May 1, 2025
• Last Updated: April 2, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share