ISHLT consensus on clinically meaningful endpoints for lung transplant trials

Consensus recommendations from the International Society for Heart and Lung Transplantation (ISHLT) on the selection of clinically meaningful endpoints for lung transplant clinical trials were published in The Journal of Heart and Lung Transplantation by Greenland et al. An international, multidisciplinary working group was convened to develop consensus, using a structured, three-round Delphi process, on considerations and definitions for trial endpoints beyond mortality, and to outline best practices for their implementation. 

Key data: Grade 3 primary graft dysfunction (PGD3) 48 or 72 hours after transplant is a validated primary endpoint, although trials should clearly define whether patients requiring extracorporeal life support (ECLS) are included in PGD endpoints. Chronic lung allograft dysfunction (CLAD) onset and progression are preferred primary endpoints for prevention and treatment trials, respectively. ISHLT Grade ≥A2 or Grade ≥A1 (forced expiratory volume in one second [FEV1] decline ≥10% from baseline or other evidence of graft injury) are appropriate acute cellular rejection (ACR) endpoints; however, ACR is a less clinically meaningful endpoint than CLAD. Clinical trials expected to impact patient function/feeling should include at least one lung transplant- or respiratory-specific patient-reported outcome (PRO) where feasible, infection endpoints should be standardized and prospectively defined, and children should be enrolled at a minimum for pharmacokinetic (PK) and safety assessments.

Key learning: Standardized endpoints in lung transplant trials may support consistency in trial design and accelerate development of therapies to improve lung transplant outcomes.