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

CMV Infection Clinical Trial

Official title:

Efficacy and Safety of Prophylactic Use of Letermovir Versus Preemptive Strategy in Kidney Transplant Recipients at Higher Risk of Cytomegalovirus Infection: a Prospective Randomized Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06341686
• Other study ID #: 75471023.2.0000.0082
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 5, 2024
• Est. completion date: May 2025

Study information

• Verified date: March 2024
• Source: Hospital do Rim e Hipertensão
• Contact: Hélio Tedesco
• Phone: +55 11 5087 8113
• Email: heliotedesco[@]medfarm.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: May 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

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

Related Conditions & MeSH terms

• CMV Infection
• Communicable Diseases
• Cytomegalovirus Infections
• Infections

Intervention

Drug:
• Letermovir 480 MG
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
• Ganciclovir
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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospital do Rim e Hipertensão

References & Publications (8)

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 — View Citation

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 Rec — View Citation

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 r — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 Tr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of CMV syndrome or disease	Proportion (%) of CMV syndrome or disease	6 months after transplantation
Secondary	Incidence of patients with plasma CMV DNAemia > 200 IU	Proportion (%) of patients with plasma CMV DNAemia > 200 IU	3 months
Secondary	Incidence of patients with CMV infection/syndrome/disease	Proportion (%) of patients with CMV infection/syndrome/disease	84 Days