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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Infections, Cytomegalovirus

Intervention / Treatment
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* Drug: Letermovir 240 mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria (retrospective cohort): HIV-infected patients. Patients with multivisceral transplant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Clinical trial of a prospective cohort compared to a retrospective (historical control) cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letermovir (prospective cohort)<br>2 tablets of 240 milligrams (mg) Letermovir orally once daily. during 12 months | Drug: Letermovir 240 mg Oral Tablet<br>* 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.<br>|
| No Intervention: Valganciclovir (retrospective cohort)<br>Retrospective cohort, of patients treated with Valganciclovir during 12 months | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of CMV disease/replication | 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. | During 12 months after initiation of prophylaxis | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung transplant, CMV prophylaxis, Cytomegalovirus