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
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 100
- Primary Endpoint
- Incidence of CMV syndrome or disease
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Letermovir
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.
Intervention: Letermovir 480 MG (Drug)
Preemptive therapy
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.
Intervention: Ganciclovir (Drug)
Outcomes
Primary Outcomes
Incidence of CMV syndrome or disease
Time Frame: 6 months after transplantation
Proportion (%) of CMV syndrome or disease
Secondary Outcomes
- Incidence of patients with plasma CMV DNAemia > 200 IU(3 months)
- Incidence of patients with CMV infection/syndrome/disease(84 Days)
Investigators
Helio Tedesco Silva Junior
Investigador Principal
Hospital do Rim e Hipertensão