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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pleural Effusion Disorder
• Intervention / Treatment: Procedure: Ultrasoinc elastography-guided pleural biopsy followed by as-needed medical thoracoscopic pleural biopsy; Procedure: Semi-rigid thoracoscopic pleural biopsy

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mingming Deng; Phone Number: +86 18801336854; Email: isdeng1017@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • China-Japan Friendship Hospital
      • Contact: Mingming Deng; Phone Number: +86 18801336854; Email: isdeng1017@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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;
2. Hemodynamic instability;
3. Refractory hypoxemia despite supplemental oxygen;
4. 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;
5. Pleural effusion conclusively identified as a transudate;
6. Pregnancy or lactation;
7. Any condition that, in the investigator's judgment, would compromise protocol compliance or follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Step-up strategy; Participants in this arm will first undergo ultrasound elastography-guided pleural biopsy (UEPB) under local anaesthesia. If the biopsy specimen is non-diagnostic, participants will proceed to semi-rigid medical thoracoscopic pleural biopsy under local anaesthesia or moderate sedation.	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.
Active Comparator: Immidiate semi-rigid thoracoscopy; Participants in this arm will undergo semi-rigid medical thoracoscopic pleural biopsy as the initial and sole diagnostic procedure. The procedure is performed under local anaesthesia or moderate sedation. Biopsy specimens are obtained under direct visualization from macroscopically abnormal pleural areas.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic yield	The proportion of cases with a specific diagnosis made based on the initial biopsy (UEPB or semi-rigid thoracoscopic pleural biopsy) specimens.	7 days after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diagnostic sensitivity	The proportion of participants with a final diagnosis of specific diseases who are correctly identified by the initial biopsy method.	7 days after procedure
Diagnostic specificity	The proportion of participants with a final malignant diagnosis who are correctly identified by the initial biopsy method	7 days after procedure
The avoidance of semi-rigid thoracoscopy	The proportion of participants in the step-up arm who are diagnosed by UEPB alone and thus avoid semi-rigid thoracoscopy.	7 days after the procedure
The rate of unexpected chest tube drainage	Any chest tube placement after UEPB or prolonged chest tube drainage (>24 hours) after semi-rigid thoracoscopy.	7 days after procedure

Collaborators and Investigators

• Sponsor: China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pleural biopsy; Ultrasoinc elastography; Semi-rigid thoracoscopy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Pleural Diseases; Pleural Effusion
• Other Study ID Numbers: UPDATE-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No