Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05041426
Other study ID # STUDY21040074
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date December 6, 2021
Est. completion date July 1, 2025

Study information

Verified date March 2024
Source University of Pittsburgh
Contact Fernanda Silveira, MD
Phone 412-648-6512
Email silvfd@upmc.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is an interventional, open-label, single center, pilot study with historical controls to test the efficacy of letermovir (LET) for the prevention of CMV infection and disease in adult lung transplant recipients (LTRs) with idiopathic pulmonary fibrosis (IPF).


Description:

Approximately 30 patients with IPF listed for lung transplantation will be enrolled and 15 are expected to undergo lung transplantation during the study period and receive the intervention. Patients who are CMV seropositive will receive letermovir for 6 months, patients who are CMV seronegative and receive lungs from a CMV seropositive donor (CMV D+/R-) will receive letermovir for 12 months. All patients will be followed for 12 weeks after completion of letermovir for the occurrence of CMV infection or disease after prophylaxis. Historical controls will be LTRs for IPF from 2010-2019 who are CMV R+ or CMV D+/R- (donor positive/recipient negative). CMV prophylaxis in the historical controls was with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-. Patients will be matched for CMV serostatus, induction immunosuppression, age, and telomere length.


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date July 1, 2025
Est. primary completion date July 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility Inclusion Criteria: - Age =18 years on day of signing informed consent - Listed for lung transplantation (single or double) due to a diagnosis of IPF or receipt of a lung transplant (single or double) for IPF in the 72 hours prior to enrollment - Have a documented positive serostatus for CMV (CMV IgG seropositive, R+) - Have a documented negative serostatus for CMV (CMV IgG seronegative, R-) and anticipate receiving or having received a lung allograft from a CMV IgG positive donor, D+). Only participants who are R+ or who are CMV D+/R- will receive intervention. Participants who are CMV D-/R- will be considered screen failures - Able to travel to UPMC for routine post-transplant visits for a minimum of 15 months after transplantation - Able to provide informed consent - Be willing to use a contraceptive method while receiving LET and for at least 90 days following last dose of LET Exclusion Criteria: - Receipt of a previous solid organ transplant or hematopoietic stem cell transplant - Multi-organ transplant recipient, i.e., heart-lung or lung-liver - HIV seropositive - HCV antibody or HCV RNA positive - Donor HCV NAT positive - Anticipated need for use of ganciclovir, valganciclovir, foscarnet, or cidofovir at the time of transplant - Known or suspected hypersensitivity to LET or acyclovir - CrCl < 10 ml/min or dialysis on day of transplant - Child-Pugh Class C severe hepatic insufficiency - Pregnancy or expected to conceive while on LET and through at least 90 days following cessation of LET

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Letermovir
Participants who are CMV R+ will receive LET prophylaxis for 6 months, and participants who are CMV D+/R- will receive LET prophylaxis for 12 months. The duration of prophylaxis is per current standard of care. LET will be administered at a dose of 480 mg IV or oral once daily. IV administration will occur only for those patients unable to swallow tablets. If LET is co-administered with cyclosporin A (CsA), the dosage of LET should be decreased to 240 mg once daily. All patients will be followed for 12 weeks after completion of LET for the occurrence of CMV infection or disease after prophylaxis. Participants on this protocol will receive acyclovir 400 mg orally BID for the duration of LET therapy for herpes simplex virus and varicella zoster virus prophylaxis.
Valganciclovir
Historical controls will have received CMV prophylaxis with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-.

Locations

Country Name City State
United States UPMC Pittsburgh Pennsylvania
United States UPMC Pittsburgh Pennsylvania

Sponsors (2)

Lead Sponsor Collaborator
Fernanda P Silveira, MD, MS Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Occurrence of CMV infection or disease during prophylaxis Proportion of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease during letermovir prophylaxis. This will be compared to the proportion of CMV infection or disease in historical lung transplant recipients with idiopathic pulmonary fibrosis who received valganciclovir prophylaxis 6-12 months post-transplant
Primary Occurrence of CMV infection or disease in the 3 months following completion of prophylaxis Proportion of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease in the 3 months following completion of prophylaxis with letermovir. This will be compared to the proportion of CMV infection or disease in the 3 months following in historical lung transplant recipients with idiopathic pulmonary fibrosis who received valganciclovir prophylaxis. 12 weeks after completion of letermovir
Secondary Discontinuation events Discontinuation of letermovir will be compared to discontinuation of valganciclovir in historical controls 6-12 months
Secondary Occurrence of leukopenia or neutropenia while on prophylaxis Proportion of participants who develop any of the following while receiving letermovir: total WBC count = 3,500 cells/mL or absolute neutrophil count = 1,000 cells/mL. This will be compared to the rate of total WBC count = 3,500 cells/mL or absolute neutrophil count = 1,000 cells/mL in historical controls while receiving valganciclovir prophylaxis. 6-12 months
See also
  Status Clinical Trial Phase
Recruiting NCT05404919 - Utilization of Hepatitis B Virus NAT+ Donors for Hepatitis B Vaccinated Lung Transplant Candidates Phase 2
Completed NCT03299504 - Factors Predicting Success in Lung Transplant Recipients Who Have Undergone Intensive Post-operative Rehabilitation
Completed NCT00755781 - Study of Cyclosporine Inhalation Solution (CIS) in Improving Bronchiolitis Obliterans Syndrome-Free Survival Following Lung Transplantation Phase 3
Recruiting NCT05547698 - A Study of Venoarterial ECMO vs Off-Pump Bilateral Orthotopic Lung Transplantation N/A
Terminated NCT03207399 - Lung Transplantation in Chronic HCV Infection With Post Transplant EPCLUSA Treatment Phase 4
Completed NCT03300882 - PREDICT Cytomegalovirus (CMV)
Recruiting NCT05101460 - An All Comers Registry For Normothermic Ex Vivo Lung Perfusion (EVLP) as Assessment of Donor Lungs for Transplant
Completed NCT03150095 - Health Coaching to Improve Self-Management in Thoracic Transplant Candidates N/A
Completed NCT04420195 - Envarsus XR in Lung Transplant Phase 2
Recruiting NCT02235610 - Use of Ex Vivo Lung Perfusion (EVLP) in Reconditioning Marginal Donor Lungs for Transplantation N/A
Not yet recruiting NCT06066229 - Identification of Patient Important Outcomes in Lung Transplantation
Recruiting NCT04601818 - Planned Semi-Elective Lung Tx Study N/A
Recruiting NCT03072589 - Study to Evaluate Adenosine 2A Receptor Agonist (Regadenoson) in Patients Undergoing Lung Transplantation Phase 1
Completed NCT01963780 - International EXPAND Lung Pivotal Trial N/A
Recruiting NCT05671887 - DREAM: Double Lung Transplant REgistry Aimed for Lung-limited Malignancies
Completed NCT03987113 - Impact of Cold Ischemia on Pulmonary Endothelial Dysfunction in Ex-vivo Pulmonary Reconditioning
Recruiting NCT02748798 - Developing Optimal Parameters for Hyperpolarized Noble Gas and Inert Fluorinated Gas MRI of Lung Disorders Early Phase 1
Completed NCT03167528 - Contribution of Learning and Practice of Different Complementary Therapies in Pulmonary Transplant Patients N/A
Active, not recruiting NCT04244734 - Implementation of an Early Rehabilitation Program for the Patient With Lung Transplantation: From the ICU to Home. N/A
Active, not recruiting NCT01365429 - Novel Lung Trial: Normothermic Ex Vivo Lung Perfusion (Evlp) As An Assessment Of Extended/Marginal Donor Lungs N/A