Confocal Laser Endomicroscopy Guided Medical Thoracoscopy for the Diagnosis of Pleural Disease

Efficacy and Safety of Confocal Laser Endomicroscopy Guided Medical Thoracoscopy for the Diagnosis of Pleural Disease: a Multicenter Randomized Controlled Trial

A prospective multicenter randomized controlled trial was conducted to evaluate the efficacy and safety of thoracoscopic biopsy guided by confocal optical real-time microscopic imaging (nCLE) in the diagnosis of fibrinal pleurisy of unknown etiology. Patients with fibrinous pleurisy of unknown etiology who were to undergo thoracoscopic pleural biopsy were enrolled and informed consent was signed. Subjects were randomized to either the nCLE guided biopsy Group (Group A) or the visual biopsy group (Group B) according to the randomization table (1:1 ratio). nCLE was used to probe the benign and malignant status of pleural lesions, compare the consistency of random pathological biopsy or nCLE guided biopsy with histopathological results, compare whether nCLE guided biopsy can reduce the number of thoracoscopic biopsies, and follow up short-term postoperative complications to evaluate its safety.

Study Overview

• Status: Recruiting
• Conditions: Pleural Diseases; Pleural Effusion
• Intervention / Treatment: Procedure: Confocal laser endomicroscopy guided pleural biopsy using medical thoracoscopy; Procedure: Plerual biopsy using medical thoracoscopy

• Study Type: Interventional
• Enrollment (Estimated): 158
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gang Hou; Phone Number: 13840065481; Email: hougangcmu@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • Recruiting
      • 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:

• Age ≥ 18 years;
• Evidence of exudative pleural effusion in which a specific diagnosis could not be determined using clinical, radiological, laboratory, or cytological examinations
• Willingness to participate in the study and undergo an invasive procedure.;

Exclusion Criteria:

• Pleural thickening or pleural-based mass without pleural effusion on radiologic examination;
• Hemodynamic instability;
• Presence of parapneumonic effusion;
• Any contraindication to pleural biopsy or semirigid thoracoscopy;
• Participation in other studies within three months without withdrawal or termination.

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: pCLE guided pleural biopsy via semi-rigid thoracoscopy; pCLE will be introduced to detect suspected areas of the parietal pleura. The pCLE inspection will follow a standardized protocol with two main steps. First, any visible abnormalities under white light, such as nodules or thickening, will be examined with pCLE to evaluate intralesional heterogeneity and determine the best biopsy site. Second, the basal pleura will be systematically swept, covering at least two intercostal spaces above the costophrenic recess, including the diaphragmatic pleura and lower posterior chest wall, which are common sites for malignant involvement. After confirming the targeted area of the parietal pleura for pleural biopsy, the pCLE probe will be withdrawn, and a flexible forceps biopsy will be performed. This process will be repeated eight times, and eight samples will be obtained. All specimens will be transported in separate formalin containers with biopsy sequences for histopathological analysis.	Procedure: Confocal laser endomicroscopy guided pleural biopsy using medical thoracoscopy; After the completion of the routine thoracoscopic examination, the biopsy location was determined based on the results of chest CT/ ultrasound. The benign and malignant states of pleural lesions were explored by nCLE and image records were collected. Then, the biopsy tissues were collected under the guidance of nCLE.
Placebo Comparator: Conventional Pleural biopsy via semi-rigid thoracoscopy; For patients assigned to receive pleural biopsy via semi-rigid thoracoscopy alone, the parietal, visceral, and diaphragmatic pleura will be inspected, and eight biopsies will be obtained under direct vision in all suspected areas of the parietal pleura.	Procedure: Plerual biopsy using medical thoracoscopy; After the completion of the routine thoracoscopic examination, the biopsy location was determined according to the results of chest CT/ ultrasound, and random pathological biopsy was performed, and biopsy tissues were collected by biopsy forceps.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic yield	The proportion of participants in whom a specific diagnosis is established following pleural biopsy via semirigid thoracoscopy, based on histopathological analysis and final reference diagnosis (including 12-month follow-up for initially benign or nonspecific results).	Up to 12 months after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative likelihood ratio	The negative likelihood ratio is defined as the probability of a negative biopsy result (i.e., no specific malignant or tuberculous diagnosis) in a patient who truly has the target disease (malignant pleural mesothelioma, metastatic cancer, or tuberculous pleurisy), divided by the probability of a negative biopsy result in a patient who does not have the disease. Because pleural biopsy results have no false positives in this study (specificity = 1, false-positive rate = 0), the NLR simplifies to 1 - sensitivity. It will be calculated using the final reference diagnosis at 12 months as the gold standard.	Up to 12 months after the procedure
Diagnostic sensitivity for specific diseases	Sensitivity of the procedure for diagnosing malignant pleural mesothelioma, metastatic cancer, and tuberculous pleurisy, as determined by the reference standard.	Up to 12 months after the procedure
Procedural time	Total duration of the thoracoscopic procedure from insertion to removal of the thoracoscope.	Day of procedure
Rate of adequate specimens for achieving molecular diagnosis	Proportion of biopsy specimens that are sufficient for predictive molecular marker analysis according to tumor type (e.g., PD-L1, EGFR, ALK, ROS-1, HER2, ER, PR, BRCA, RAS, BRAF, etc.). Specimens are categorized as: (a) successful molecular marker analysis, (b) unsuccessful molecular marker analysis (explicit test failure), (c) not sent despite relevance.	Within 2 weeks after the procedure (upon pathological reporting)
Incidence of procedure-related complications	Occurrence of any adverse events related to the procedure, including but not limited to: prolonged air leak, hemorrhage (graded as nil/slight self-limiting, mild requiring local vasoactive medication, moderate-to-severe requiring electrocautery or argon plasma coagulation), subcutaneous emphysema, postoperative fever, empyema, wound infection, cardiac arrhythmias, hypotension, and chest wall seeding from mesothelioma.	From start of procedure up to 30 days post-procedure (or until chest tube removal and hospital discharge, whichever is longer)
Sampling quality (tissue depth and interpretability)	Tissue depth: Biopsy quality determined based on tissue depth (e.g., deep biopsy including fatty tissue from the thoracic wall is considered high quality). Interpretability: Assessed as (a) easily interpretable (sufficient tissue with all diagnostic elements), (b) interpretable with some difficulty, (c) interpretable with great difficulty, (d) non-interpretable.	Within 2 weeks after the procedure (upon pathological assessment)

Collaborators and Investigators

• Sponsor: China-Japan Friendship Hospital
• Collaborators: Henan Provincial People's Hospital; The Second Affiliated Hospital of Harbin Medical University; Anhui Chest Hospital; Shandong Public Health Clinical Center; Shanghai Rui Jin Hospital; Wuhan Pulmonary Hospital; The Second People's Hospital of Gansu Province

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Pleural Effusion; Pleural Diseases
• Other Study ID Numbers: 2022YFC2404404-3-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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