Ultrasounic Elastography-guided Pleural Biopsy Followed by As-needed Medical Thoracoscopic Pleural Biopsy Versus Immediate Medical Thoracoscopic Pleural Biopsy for the Diagnosis of Pleural Effusion

Overview

Brief Summary The goal of this clinical trial is to determine whether an initial diagnostic approach using ultrasound elastography-guided pleural biopsy (UEPB) is non-inferior to immediate medical thoracoscopic pleural biopsy in terms of diagnostic yield for obtaining a definitive histopathological diagnosis in patients with exudative pleural effusion of unclear etiology. The main questions it aims to answer are: Is the step-up strategy (UEPB first, reserving thoracoscopy for non-diagnostic cases) non-inferior to immediate medical thoracoscopy in diagnostic yield? Does the step-up strategy provide advantages in safety, patient tolerance, hospital stay, and cost-effectiveness compared to immediate thoracoscopy? Researchers will compare a step-up strategy (initial UEPB, followed by medical thoracoscopy if UEPB is non-diagnostic) versus immediate medical thoracoscopic pleural biopsy to see if the step-up approach achieves comparable diagnostic accuracy while potentially reducing procedure-related burden and healthcare resource use. Participants will: Be randomly assigned in a 1:1 ratio to either the step-up strategy arm or the immediate medical thoracoscopy arm. If assigned to the step-up arm: undergo UEPB under local anesthesia; if the biopsy is non-diagnostic, proceed to semi-rigid medical thoracoscopy. If assigned to the immediate thoracoscopy arm: undergo semi-rigid medical thoracoscopic pleural biopsy as the initial and sole diagnostic procedure. Provide tissue samples for histopathological, immunohistochemical, and molecular analyses as clinically indicated. Complete short-term follow-up at 7 days post-procedure (by telephone or clinic visit) to monitor adverse events and symptom recovery. If initially diagnosed with non-specific benign disease or remain undiagnosed, complete a long-term follow-up at 12 months to establish a final diagnosis.

Interventions

• Procedure Ultrasoinc elastography-guided pleural biopsy followed by as-needed medical thoracoscopic pleural biopsy
  Participants receive ultrasound elastography-guided pleural biopsy (UEPB) as the first diagnostic procedure. If the UEPB specimen is non-diagnostic, participants proceed to semi-rigid medical thoracoscopic pleural biopsy.
• Procedure Semi-rigid thoracoscopic pleural biopsy
  Participants receive semi-rigid medical thoracoscopic pleural biopsy as the initial and sole diagnostic procedure. The procedure is performed under local anaesthesia or moderate sedation, with biopsies obtained under direct visualization. A chest tube is inserted prophylactically following biopsy; chemical pleurodesis may be performed during the same procedure if clinically indicated.

Primary outcome measures

• Diagnostic yield [Time frame: 7 days after the procedure]

Secondary outcome measures (4)

• diagnostic sensitivity [Time frame: 7 days after procedure]
• Diagnostic specificity [Time frame: 7 days after procedure]
• The avoidance of semi-rigid thoracoscopy [Time frame: 7 days after the procedure]
• The rate of unexpected chest tube drainage [Time frame: 7 days after procedure]

Eligibility criteria

Inclusion criteria

• Age ≥18 years;
• Patients with exudative pleural effusion of unknown origin;
• Patients with negative pleural fluid cytology results;
• Patients who had not undergone pleural biopsy before enrolment.

Exclusion criteria

• Significantly bleeding risk, including uncorrectable coagulopathy (such as INR >1.5, platelet count <50×109 /L) or the need for ongoing anticoagulant/antiplatelet therapy that cannot be safely paused;
• Hemodynamic instability;
• Refractory hypoxemia despite supplemental oxygen;
• Any severe concurrent illness or cardiopulmonary compromise that, in the investigator's judgment, makes either procedural sedation (for thoracoscopy) or a bedside biopsy (for UEPB) unsafe;
• Pleural effusion conclusively identified as a transudate;
• Pregnancy or lactation;
• Any condition that, in the investigator's judgment, would compromise protocol compliance or follow-up.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

China · 1 center

• China-Japan Friendship Hospital — Beijing

Publications

• Liao L, Ma J, Ni J, Lin J, Zhao S, Xia Y, Liu X, Deng M, Zheng Z, Hou G. Ultrasonic elastography-guided pleural biopsy followed by as-needed semi-rigid thoracoscopic pleural biopsy versus immediate semi-rigid thoracoscopic pleural biopsy for the diagnosis of pleural effusion (UPDATE-3): a protocol of randomised controlled trial. Respir Res. 2026 Jun 20. doi: 10.1186/s12931-026-03772-6. Online ahea PMID 42321816

Identifiers

NCT: NCT07419620 · UPDATE-3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗