CMV, Lung Transplant
Conditions
Keywords
Lung transplant, CMV, Letermovir
Brief 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).
Detailed 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.
Interventions
DRUGLetermovir
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.
DRUGValganciclovir
Historical controls will have received CMV prophylaxis with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-.
Sponsors
Fernanda P Silveira, MD, MS
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Interventional, open-label, single center, pilot study with historical controls
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of CMV Infection or Disease During Prophylaxis | 6-12 months post-transplant | Number of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease during letermovir prophylaxis. |
| Occurrence of CMV Infection or Disease in the 3 Months Following Completion of Prophylaxis | 12 weeks after completion of letermovir | Number of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease in the 3 months following completion of prophylaxis with letermovir. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Discontinuation Events | 6-12 months | Discontinuation of letermovir due to adverse events or intolerability |
| Occurrence of Leukopenia or Neutropenia While on Prophylaxis | 6-12 months | Number 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFernanda Silveira
University of Pittsburgh
Participant flow
Recruitment details
Patients with idiopathic pulmonary fibrosis who are active on the lung transplant or within the first 72 hours post-transplant could be enrolled.
Pre-assignment details
The initial intent was to compare the letermovir group to historical controls from a separate cohort, who received valganciclovir prophylaxis; however, we did not have access to this data.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62 Years |
| Bilateral lung transplant | 15 Participants |
| CMV serostatus CMV Donor Positive Recipient Negative | 6 Participants |
| CMV serostatus CMV seropositive | 9 Participants |
| Induction Alemtuzumab | 1 Participants |
| Induction Basiliximab | 13 Participants |
| Induction Thymoglobulin | 1 Participants |
| Region of Enrollment United States | 15 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 15 |
| other Total, other adverse events | 2 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
None listed