First Local Anaesthesia Thoracoscopy for Pleural Effusion Diagnosis. (FLAT)

Local Anesthesia Thoracoscopy as a First Line Approach in the Diagnosis of Suspected Malignant Pleural Effusion: FLAT Trial.

Non randomized study with two groups. The study group includes patients with suspected malignant pleural effusion, in whom the investigation of pleural effusion begins directly with pleural biopsy by Local Anesthesia Thoracoscopy (LAT).

The Control Group includes patients who come to the same hospital and are treated with the Standard of Care (SOC) strategies were used. Efficacy of LAT, Sensitivity, Hospitalization, time to diagnosis and general safety and comfort of the groups' subjects will be assessed.

Study Overview

• Status: Recruiting
• Conditions: Mesothelioma, Malignant; Pleural Effusion, Malignant; Pleural Effusion; Suspected Malignant Lung Neoplasm
• Intervention / Treatment: Procedure: Local Anesthesia Thoracoscopy; Device: Pleuroscopy with Rigid Thoracoscope and Forceps biopsies

Detailed Description

Diagnostic approach of patients with with unexplained lymphocytic exudate is the main subject of the study. Minimally invasive techniques (single entry thoracoscopy with local anesthesia -LAT) have been developed for the definitive biopsy of the parietal pleura, with which, in addition to the diagnosis, a therapeutic pleurodesis can be performed at the same time. Usually, diagnostic LAT is performed only after 3 negative pleural fluid cytological tests have been performed, thus delaying the diagnostic access and treatment of the patient.

The aim of this study is to evaluate the conventional diagnostic approach used in daily clinical practice (3 consecutive punctures of pleural effusion with cytological examination and in case of insufficient diagnosis pleural biopsy, either LAT or VATS depending on the clinical assessment of the patient) with the simplest immediate performance of LAT as soon as a pleural effusion suspected of malignancy is detected. Thus two subject groups will be compared. The first (LAT Group) will undergo Local Anesthesia Thoracoscopy as the first line option for the diagnosis of the suspected MPE. The control group will undergo the standard of care recommended guidelines for the diagnosis of MPE.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nektarios ANAGNOSTOPOULOS, Ass. professor; Phone Number: +306946869480; Email: aris.anag@yahoo.gr
• Study Contact Backup: Name: Michail Kon/nos Tsatsis, MD, MSc, PhDc; Phone Number: +306979234105; Email: tsatsis.mihail@gmail.com

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 11527
      • Recruiting
      • Sotiria General Hospital of Thoracic Diseases
      • Contact: Nektratios Anagnostopoulos, Ass. Professor; Phone Number: +306946869480; Email: aris.anag@yahoo.gr
      • Contact: Michail Kon/nos Tsatsis, MD, MSc, PhD(c)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Undiagnosed pleural effusion with the character of a lymphocytic exudate

Exclusion Criteria:

• Empyema
• Transudate pleural effusion.
• Central airway obstruction by tumor.
• Existence of extensive adhesions that do not allow the development of iatrogenic pneumothorax and the safe entry of the thoracoscope.
• Uncontrollable cough.
• Acute respiratory failure and/or Hypercapnia.
• Performance Status: 5

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LAT Group; The study group includes patients in whom the investigation of pleural effusion begins directly with pleural biopsy by Local Anesthesia Thoracoscopy (LAT) under conscious sedation. In these patients, imaging with chest CT and/or thoracic ultrasound has been performed and lymphocytic exudate is confirmed in fluid aspiration.	Procedure: Local Anesthesia Thoracoscopy; The patient is placed in a lateral decubitus, with the affected hemithorax upwards. Ensuring a venous line and full monitoring of vital functions. Mild sedation is given and a dose of Ceftriaxone is given 30 minutes before. Local anesthesia is injected in layers, starting from the skin and working up to the intercostal muscles, intercostal nerve, and periosteum of the rib. Development of pneumothorax is done using a 16-gauge Boutin needle. 15 spontaneous breaths are sufficient to create a pneumothorax, and entry of rigid thoracoscope into the hemithorax through a 11-13 mm Trocar. Multiple biopsies from the parietal pleura are taken and pleurodesis is made according to operator judgment. A chest drain 20-22 G is placed and sutured. A chest X-ray is performed 2-8 hours later after the patient is transferred to the ward. Chest drain is removed after 24h if fluid production is <250ml and lung re-expansion.; Device: Pleuroscopy with Rigid Thoracoscope and Forceps biopsies; A video thoracoscope with an external light source, outer diameter 10 mm (Karl Storz), is inserted into the pleural cavity through a uniportal incision (1 - 1.5 cm) and complete inspection of the pleural cavity is performed. Parietal pleural biopsies are taken with a rigid 40 mm forceps (Karl Storz).
No Intervention: Control Group; The Control Group includes patients admitted with undiagnosed pleural lymphocytic exudate, who undergo Standard of Care (SOC) diagnostic strategies according to BTS guideline including among others, 3 samples for cytological examination (40-60 ml each), chest tube drainage, microbiological and immunological studies. If the diagnosis is not established and there is still indication for pleural biopsy patients are referred either for surgical biopsy or LAT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Diagnosis	Time to diagnosis is defined as the period between the first thoracentesis ,showing a lymphocytic exudate, of a newly discovered pleural effusion in a patient without prior signs of pleural disease to the time of multi-disciplinary team final diagnosis involving a pathology report of biopsy samples.	From enrollment to final diagnosis of MDT, assesed up to 12 months
Hospitalization time	The time from the patient's admission in the hospital with diagnosis of unexplained lymphocytic pleural effusion until discharge with or without final diagnosis.	From enrollment to hospital discharge, assesed up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's discomfort/pain	A Visual Analogue Scale (VAS) measures the intensity of pain the patient feels after the intervention (Medical Thoracoscopy vs Surgical Biopsy). A horizontal line ranging from 0 to 10, (0=No pain, 10=Extreme pain), is used. The patient is examined every day, until his discharge and is asked to mark on the line his respective level of discomfort/pain.	Day 1: immediately post-procedure. Day 2: 24hours post-procedure. Day 3 up to Day of tube removal: Every 24 hours. Time frame ends on removal of chest tube or patient dishcarge, assesment up to 2 weeks
Complications	We compare the rate of post interventional complications across the two groups (Surgical biopsy vs LAT)	Day 1: immediately post-procedure. Day 2: 24hours post-procedure. Day 3 up to Day of tube removal: Every 24 hours. Time frame ends on removal of chest tube or patient dishcarge, assesment up to 3 months.
Rate of Non Specific Pleuritis	We aim to asses wheter the rate of positive pleural biopsies for non specific pleuritis differed significantly between Surgical biopsy group and LAT group.	Assesment up to 12 months

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: Sotiria Thoracic Diseases Hospital of Athens
• Investigators: Study Director: Grigorios Stratakos, Professor, National and Kapodistrian University of Athens

Publications and helpful links

General Publications

• Arnold DT, De Fonseka D, Perry S, Morley A, Harvey JE, Medford A, Brett M, Maskell NA. Investigating unilateral pleural effusions: the role of cytology. Eur Respir J. 2018 Nov 8;52(5):1801254. doi: 10.1183/13993003.01254-2018. Print 2018 Nov.
• Ferguson J, Tsim S, Kelly C, Alexander L, Shad S, Neilly M, Tate M, Zahra B, Saleh M, Cowell G, Banks E, Grundy S, Corcoran J, Downer N, Stanton A, Evison M, Rahman NM, Maskell N, Blyth KG. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): protocol of a prospective, multicentre, observational study. BMJ Open Respir Res. 2023 Nov 23;10(1):e001771. doi: 10.1136/bmjresp-2023-001771.
• Wan YY, Zhai CC, Lin XS, Yao ZH, Liu QH, Zhu L, Li DZ, Li XL, Wang N, Lin DJ. Safety and complications of medical thoracoscopy in the management of pleural diseases. BMC Pulm Med. 2019 Jul 10;19(1):125. doi: 10.1186/s12890-019-0888-5.
• Shaikh F, Lentz RJ, Feller-Kopman D, Maldonado F. Medical thoracoscopy in the diagnosis of pleural disease: a guide for the clinician. Expert Rev Respir Med. 2020 Oct;14(10):987-1000. doi: 10.1080/17476348.2020.1788940. Epub 2020 Jul 12.
• Gong L, Huang G, Huang Y, Liu D, Tang X. Medical Thoracoscopy for the Management of Exudative Pleural Effusion: A Retrospective Study. Risk Manag Healthc Policy. 2020 Dec 4;13:2845-2855. doi: 10.2147/RMHP.S287758. eCollection 2020.
• Murthy V, Bessich JL. Medical thoracoscopy and its evolving role in the diagnosis and treatment of pleural disease. J Thorac Dis. 2017 Sep;9(Suppl 10):S1011-S1021. doi: 10.21037/jtd.2017.06.37.
• Xu LL, Yang Y, Wang Z, Wang XJ, Tong ZH, Shi HZ. Malignant pleural mesothelioma: diagnostic value of medical thoracoscopy and long-term prognostic analysis. BMC Pulm Med. 2018 Apr 3;18(1):56. doi: 10.1186/s12890-018-0619-3.
• Li D, Jackson K, Panchal R, Aujayeb A. Local Anaesthetic Thoracoscopy for Pleural Effusion-A Narrative Review. Healthcare (Basel). 2022 Oct 9;10(10):1978. doi: 10.3390/healthcare10101978.
• Kiani A, Abedini A, Karimi M, Samadi K, Sheikhy K, Farzanegan B, Pour Abdollah M, Jamaati H, Jabardarjani HR, Masjedi MR. Diagnostic Yield of Medical Thoracoscopy in Undiagnosed Pleural Effusion. Tanaffos. 2015;14(4):227-31.
• Wu YB, Xu LL, Wang XJ, Wang Z, Zhang J, Tong ZH, Shi HZ. Diagnostic value of medical thoracoscopy in malignant pleural effusion. BMC Pulm Med. 2017 Aug 4;17(1):109. doi: 10.1186/s12890-017-0451-1.
• Kassirian S, Hinton SN, Cuninghame S, Chaudhary R, Iansavitchene A, Amjadi K, Dhaliwal I, Zeman-Pocrnich C, Mitchell MA. Diagnostic sensitivity of pleural fluid cytology in malignant pleural effusions: systematic review and meta-analysis. Thorax. 2023 Jan;78(1):32-40. doi: 10.1136/thoraxjnl-2021-217959. Epub 2022 Feb 2.
• Tsim S, Paterson S, Cartwright D, Fong CJ, Alexander L, Kelly C, Holme J, Evison M, Blyth KG. Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups. Lung Cancer. 2019 Jul;133:123-129. doi: 10.1016/j.lungcan.2019.05.017. Epub 2019 May 16.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 20, 2025
• First Posted (Actual): April 27, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 20, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Lung cancer; Mesothelioma; Malignant Pleural Effusion; Local Anesthesia Thoracoscopy; Medical Thoracoscopy; Lymphocytic Exudate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Pleural Diseases; Mesothelioma, Malignant; Lung Neoplasms; Mesothelioma; Pleural Effusion, Malignant; Pleural Effusion; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: FLAT1STIPNKUA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a preliminary study design and for confidentiality rationales in order to protect the novelty of diagnostic strategies implemented in this research .

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No