Clinical trial NCT06341686: Evaluation of the Prophylactic Use of Letermovir in Kidney Transplant Recipients at Risk of Cytomegalovirus Infection
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: CMV Infection
Keywords: Cytomegalovirus
Letermovir
Kidney transplant
Lead sponsor: Hospital do Rim e Hipertensão
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of CMV syndrome or disease
timeFrame: 6 months after transplantation
Secondary outcomes:
measure: Incidence of patients with plasma CMV DNAemia > 200 IU
timeFrame: 3 months
measure: Incidence of patients with CMV infection/syndrome/disease
timeFrame: 84 Days
Other outcomes:
Locations:
Study officials:
affiliation: Doctor of Renal Transplant Unit
name: Helio Tedesco
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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 Recipients Without Pharmacological Prophylaxis. Transplantation. 2020 Oct;104(10):2139-2147. doi: 10.1097/TP.0000000000003124.
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 receiving preemptive therapy. Transpl Infect Dis. 2019 Dec;21(6):e13106. doi: 10.1111/tid.13106. Epub 2019 Oct 29.
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 no pharmacological prophylaxis. J Bras Nefrol. 2017 Oct-Dec;39(4):413-423. doi: 10.5935/0101-2800.20170074. English, Portuguese.
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.
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 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.
citation: 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.