The diagnosis of exudative pleural effusion is challenging. Although ultrasound-guided pleural biopsy (UGBx) is common, its effectiveness varies, especially in the absence of pleural abnormalities. New imaging techniques have been explored to improve UGBx outcomes, but the results remain inadequate. Recently, needle-based confocal laser endomicroscopy (nCLE) has been used to improve biopsy targeting and diagnostic yield through real-time cellular-level imaging; however, robust evidence is lacking. This trial aims to assess the diagnostic yield and safety of nCLE-assisted UGBx for unknown exudative pleural effusions. COLLABORATION-II is a multicenter randomized controlled study in China involving 324 participants across ten centers. Participants will be divided into two groups based on the ultrasound findings: Group 1 with pleural thickening (> 5 mm) and/or pleural nodularity, and Group 2 with thickness ≤ 5 mm and no nodularity. Each group will be randomly assigned to either the nCLE-assisted UGBx or UGBx arm at a 1:1 ratio, with a 12-month follow-up. The primary outcome is the overall diagnostic yield, while secondary outcomes include the biopsy success rate, diagnostic sensitivity for specific diseases, complication in incidence, and specimen characteristics, such as size, quality, interpretability, and adequacy for achieving molecular diagnosis. We hypothesize that the nCLE-assisted UGBx will achieve higher diagnostic yield than conventional UGBx by providing real-time, cellular-level visualization and targeted sampling of pathological areas. If this hypothesis is validated, nCLE-assisted UGBx could emerge as a novel and effective option for diagnosing patients with unknown exudative pleural effusion. This study has been registered at www.clinicaltrials.gov (Registration number: NCT07040241; Registration Date: 2025-06-26).
Zheng et al. (Thu,) studied this question.