Study Design for a Randomized Control Trial of Lung Allograft Monitoring with Blood Donor-Derived Cell-Free DNA Assessments (LAMBDA 001).

The majority of lung transplant centers in the United States perform surveillance bronchoscopy with transbronchial biopsies (TBBx) to monitor for acute rejection (AR) and infection after lung transplantation. However, no high-quality studies have assessed the benefit of surveillance TBBx, an invasive, costly procedure with a risk of complications. Donor-Derived Cell-free DNA (dd-cfDNA) is a non-invasive molecular biomarker of allograft injury that increases in the setting of AR and infection. Prior observational studies support the utility of dd-cfDNA in detecting AR and infection for surveillance purposes, however, no studies have directly compared a dd-cfDNA-based surveillance strategy to surveillance TBBx. We describe here the study design of a randomized controlled trial, Lung Allograft Monitoring with Blood dd-cfDNA Assessments (LAMBA 001) to test the hypothesis that a dd-cfDNA-based surveillance strategy is non-inferior to surveillance TBBx during the first-year post-transplant. LAMBDA 001 is a multicenter, parallel group, open label randomized controlled non-inferiority trial that aims to randomize 400 adult lung transplant recipients via stratified block randomization to surveillance with dd-cfDNA (the ProsperaTM test) vs. surveillance TBBx, performed according to the participating institution's standard of care surveillance schedule. Patients will be followed for 1-year post-transplant. The primary endpoint of the study is Hospital-Free Days (HFD) at 1 year, defined as days alive and spent outside of an acute-care hospital, long term care facility or emergency department. Secondary endpoints include forced expiratory volume in 1 second at one year, incidence of acute rejection, infection, mortality at one year, and health-related quality of life. Assuming a mean (standard deviation) HFD of 311 (37.6) days starting at 4 weeks post-transplant, a non-inferiority margin of 2% (6 HFD) and a one-sided alpha of 2.5%, a sample size of 400 patients provides 80% power to detect non-inferiority. Analysis will be run on both an intention-to-treat and per-protocol population. The LAMBDA 001 trial will provide high quality evidence comparing the effectiveness of dd-cfDNA-based surveillance vs. surveillance TBBx for lung transplant patients in the first-year post-transplant. [ABSTRACT FROM AUTHOR]