An Open-label Pilot Protocol to Evaluate the Efficacy of Letermovir for the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Lung Transplant Recipients With Idiopathic Pulmonary Fibrosis
概览
- 阶段
- 2 期
- 干预措施
- Letermovir
- 疾病 / 适应症
- Lung Transplant
- 发起方
- Fernanda P Silveira, MD, MS
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Occurrence of CMV infection or disease during prophylaxis
- 状态
- 已完成
- 最后更新
- 23天前
概览
简要总结
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).
详细描述
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.
研究者
Fernanda P Silveira, MD, MS
Professor
University of Pittsburgh
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Letermovir
Participants who are CMV seropositive (CMV R+) will receive letermovir prophylaxis for 6 months, and participants who are CMV donor seropositive/recipient seronegative (CMV D+/R-) will receive letermovir prophylaxis for 12 months. Letermovir 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 letermovir is co-administered with cyclosporine A, the dosage of letermovir will be decreased to 240 mg once daily.
干预措施: Letermovir
Valganciclovir
Historical controls will be lung transplant recipients for idiopathic pulmonary fibrosis from 2010-2019 who are CMV R+ or CMV D+/R-. CMV prophylaxis in the historical controls was with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-.
干预措施: Valganciclovir
结局指标
主要结局
Occurrence of CMV infection or disease during prophylaxis
时间窗: 6-12 months post-transplant
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
Occurrence of CMV infection or disease in the 3 months following completion of prophylaxis
时间窗: 12 weeks after completion of letermovir
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.
Occurrence of CMV Infection or Disease During Prophylaxis
时间窗: 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
时间窗: 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.
次要结局
- Discontinuation events(6-12 months)
- Occurrence of leukopenia or neutropenia while on prophylaxis(6-12 months)
- Discontinuation Events(6-12 months)
- Occurrence of Leukopenia or Neutropenia While on Prophylaxis(6-12 months)