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

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)

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."

Study Overview

• Status: Not yet recruiting
• Conditions: Infections, Cytomegalovirus
• Intervention / Treatment: Drug: Letermovir 240 mg Oral Tablet

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jose C Garrido Gracia, Ph.D; Phone Number: +34677906567; Email: josecarlos.garrido@imibic.org

Study Locations

• Spain
  • Córdoba
    • Cordoba, Córdoba, Spain, 14004
      • Hospital Universitario Reina Sofía
      • Contact: Aurora Paez Vega, Ph.D; Email: aumapave@hotmail.com
      • Principal Investigator: Julián C De la Torre Cisneros, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Collaborators: MERCK SHARP & DOHME DE ESPAÑA S.A.
• Investigators: Principal Investigator: Julián C De la Torre Cisneros, MD, Hospital Universitario Reina Sofia de Cordoba

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: September 15, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Lung transplant; Cytomegalovirus; CMV prophylaxis
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Letermovir
• Other Study ID Numbers: FCO-LET-2022-01; 2023-504384-16-00 (Other Identifier: EMA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No