LETERCOR: Efficacy of Letermovir in Preventing Cytomegalovirus (CMV) Infection in Lung Transplant Recipients vs. Valganciclovir.

Sponsor

Maimónides Biomedical Research Institute of Córdoba (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06057194

Collaborator

MERCK SHARP & DOHME DE ESPAÑA S.A. (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this quasi-experimental multicenter before-after cohort study, phase II study is to evaluate the efficacy of 12-month letermovir prophylaxis in lung transplant recipients (D+/R-) compared to a historical cohort of lung transplant recipients (D+/R-) who received 12 months of valganciclovir prophylaxis to prevent CMV disease."

Condition or Disease	Intervention/Treatment	Phase
Infections, Cytomegalovirus	Drug: Letermovir 240 mg Oral Tablet	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Clinical trial of a prospective cohort compared to a retrospective (historical control) cohort.Clinical trial of a prospective cohort compared to a retrospective (historical control) cohort.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Prospective Study to Assess the Efficacy of Letermovir Prophylaxis in Preventing CMV Infection in Lung Transplant Recipients Compared to a Retrospective Cohort Treated With Standard Valganciclovir Prophylaxis for 12 Months (LETERCOR Study)

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2027

Anticipated Study Completion Date :

Apr 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Letermovir (prospective cohort) 2 tablets of 240 milligrams (mg) Letermovir orally once daily. during 12 months	Drug: Letermovir 240 mg Oral Tablet Treatment will commence as soon as subjects can receive oral medication, with a maximum timeframe of 28 days after transplantation. If patients cannot receive oral medication after transplantation, initial prophylaxis with ganciclovir per clinical practice will be allowed. Medication will be discontinued 12 months after treatment initiation.
No Intervention: Valganciclovir (retrospective cohort) Retrospective cohort, of patients treated with Valganciclovir during 12 months

Arm

Intervention/Treatment

Experimental: Letermovir (prospective cohort)

2 tablets of 240 milligrams (mg) Letermovir orally once daily. during 12 months

Drug: Letermovir 240 mg Oral Tablet

Treatment will commence as soon as subjects can receive oral medication, with a maximum timeframe of 28 days after transplantation. If patients cannot receive oral medication after transplantation, initial prophylaxis with ganciclovir per clinical practice will be allowed. Medication will be discontinued 12 months after treatment initiation.

No Intervention: Valganciclovir (retrospective cohort)

Retrospective cohort, of patients treated with Valganciclovir during 12 months

Outcome Measures

Primary Outcome Measures

Incidence of CMV disease/replication [During 12 months after initiation of prophylaxis]
CMV replication: The term 'replication' can be used to indicate evidence of multiplication and is sometimes used interchangeably with CMV infection CMV disease: It is defined as symptomatic replication or invasive disease of organs or tissues that requires treatment at the investigator's discretion."

Secondary Outcome Measures

Antiviral prophylaxis received: [During 12 months after initiation of prophylaxis]
Doses administered of Letermovir or Valganciclovir
Dose of non anti-viral CMV Medications: Any non-antiviral therapy received as standard of care (SoC) for the management of CMV (e.g., immunoglobulins) [During 12 months after initiation of prophylaxis]
Drug Dose (mg/hour)
Administration route of non-antiviral CMV Medications: Any non-antiviral therapy received as standard of care (SoC) for the management of CMV (e.g., immunoglobulins) [During 12 months after initiation of prophylaxis]
Drug Administration Route
Duration of treatment of non-antiviral CMV Medications: Any non-antiviral therapy received as standard of care (SoC) for the management of CMV (e.g., immunoglobulins) [During 12 months after initiation of prophylaxis]
Drug treatment duration (days)
Discontinuation of non-antiviral CMV Medications: Any non-antiviral therapy received as standard of care (SoC) for the management of CMV (e.g., immunoglobulins) [During 12 months after initiation of prophylaxis]
Drug Reason for Discontinuation
Reduction of the antiviral dose related to CMV antiviral toxicity [During 12 months after initiation of prophylaxis]
Number of events of reduction
Substitution of letermovir by intravenous ganciclovir or foscarnet IV, related to CMV antiviral toxicity [During 12 months after initiation of prophylaxis]
Number of substitutions
Dose changes of immunosuppressive therapy related to CMV antiviral toxicity [During 12 months after initiation of prophylaxis]
Number of changes
Changes of immunosuppressive therapy related to CMV antiviral toxicity [During 12 months after initiation of prophylaxis]
Number of changes
Use of granulocyte colony-stimulating factors (G-CSF). [During 12 months after initiation of prophylaxis]
Number of events (use)
Incidence of leucopenia [During 12 months after initiation of prophylaxis]
Incidence of leucopenia. (leucopenia will be considered if the total leukocyte count is less than 3,000/mL)
Incidence of neutropenia [During 12 months after initiation of prophylaxis]
Incidence of leucopenia. (neutropenia will be considered if the total neutrophil count is less than 1,000/mL)
Hospital readmission associated with CMV complication [During 12 months after initiation of prophylaxis]
Number of events
Incidence of viral, bacterial, or opportunistic fungal infections during the study follow-up period. [During 12 months after initiation of prophylaxis]
Number of events
Incidence of renal toxicity directly related to CMV antivirals. [During 12 months after initiation of prophylaxis]
Number of events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria (prospective cohort):

Adults over 18 years old
Lung transplant recipients (D+/R-) pre-transplant.
Having an undetectable CMV polymerase chain reaction assay (PCR) within the 96 hours prior to the start of letermovir prophylaxis.
Patients who have provided written informed consent.

Exclusion Criteria (prospective cohort):

HIV-infected patients.
Patients with multivisceral transplant.
Patients unable to comply with the follow-up protocol.
Receiving a different antiviral prophylaxis other than ganciclovir prior to letermovir prophylaxis.
Patients with concurrent renal and hepatic insufficiency.

Inclusion Criteria (retrospective cohort):

Adults over 18 years old. Lung transplant recipients (D+/R-) pre-transplant.
Patients treated with Valganciclovir prophylaxis for 12 months.
Patients transplanted within 2 years prior to the start of the study.
Patients with a complete 13-month follow-up and comparable data to the prospective cohort to evaluate the study's primary variables.