Dual-functIon Semi-rigid thoraCoscOpy Versus semi-rigid thoracoscopy for the diagnosis of plEuRal diseases: protocol for a multicentre, open-label, randomised controlled trial in China (DISCOVER-I)

Exudative pleural effusion often presents diagnostic challenges, with up to 25% of cases remaining undiagnosed after thoracentesis or closed pleural biopsy. Semi-rigid thoracoscopy is a widely used minimally invasive diagnostic method. However, its diagnostic yield is limited by small and superficial biopsy samples due to the lack of mechanical power, particularly in cases of thickened pleura or suspected mesothelioma. We had designed and developed a dual-function semi-rigid thoracoscope and semi-rigid forceps to improve sampling quality and depth. However, their diagnostic performance and safety, particularly compared with that of conventional semi-rigid thoracoscopy is still unclear. This randomised controlled trial will enrol a total of 522 adults with exudative pleural effusions of unclear aetiology that remain undiagnosed after the initial investigations from 10 sites in China. Participants will be randomised (1:1:1) to undergo thoracoscopy using either a conventional semi-rigid thoracoscope (with flexible forceps) or a novel dual-function semi-rigid thoracoscope (with either semi-rigid forceps alone or a combination of flexible and rigid forceps). The primary outcome is diagnostic yield. Secondary outcomes include the biopsy success rate, incidence of procedure-related complications, biopsy specimen size and depth, histological interpretability, and adequacy of tissue for molecular marker analysis. We hypothesize that the dual-function semi-rigid thoracoscopy with semi-rigid forceps will achieve higher diagnostic yield than conventional semi-rigid thoracoscopy due to the larger and deeper sampling. If this hypothesis is validated, dual-function semi-rigid thoracoscopy could be a novel option for performing pleural biopsy for patients with unknown exudative pleural effusion. This study has been registered at www.clinicaltrials.gov (ID: NCT06744725; Registration Date: 2024-12-19).