Medical Thoracoscopy for Undiagnosed Transudative and Exudative Pleural Effusions

Indonesia is one of country that contributes the most cases of tuberculosis worldwide. Tuberculosis is the most commonly etiology of exudative pleural effusion. There have been many studies about undiagnosed exudative pleural effusions, but there are not many studies about the use of medical thoracoscopy for diagnosing transudative and exudative pleural effusion, especially on biomarkers of C-Reactive Protein (CRP), D-dimer, Adenosine Deaminase (ADA), Antinuclear Antibody (ANA), C3 C4 complements, Cancer Antigen 125 (CA-125), Xpert Mycobacterium Tuberculosis (Xpert MTB), Lupus Erythematosus cell (LE cell), cytology (effusion and smear) and histopathology. Information gained from those biomarkers via thoracocentesis and medical thoracoscopy, etiology of exudative and transudative pleural effusion can be detected earlier and clearly, especially etiology of infection, autoimmune, and malignancy that further can be used to reduce patients' hospitalization period, mortality, and to develop the new therapeutic agents.

Study Overview

• Status: Not yet recruiting
• Conditions: Pleural Effusion
• Intervention / Treatment: Procedure: Medical thoracoscopy; Diagnostic test: CRP, D-dimer, ADA, ANA, C3 C4 complements, CA-125, Xpert MTB, LE cell, cytology and histopathology; Drug: Lidocain, fentanyl and midazolam

Detailed Description

Medical thoracoscopy is a minimally invasive procedure to access pleura with combination of visual and medical instrument. The procedure is performed under local anesthesia and conscious sedation. Medical thoracoscopy plays role in basic diagnostic and therapeutic. The most common indication on basic diagnostic is on pleural effusion case that has primary target to get specific diagnosis when the etiology of pleural effusion is unknown. Pleural effusion is fluid accumulation inside the pleura for about 15-20 ml. Primary aim of pleural effusion diagnosis is to differentiate exudative and transudative effusions based on Light Criteria. Most of time thoracentesis cannot give etiology of exudative and transudative pleural effusion.

Researchers will evaluate subjects based on inclusion and exclusion criteria in Cipto Mangunkusumo Hospital. Research subjects will be asked for informed consent. Furthermore, data will be collected based on research form. Researchers will perform medical thoracoscopy to take specimen for analysing CRP, D-dimer, ADA, ANA, C3 C4 complements, Xpert MTB, LE cell, cytology (effusion and smear) and histopathology to detect the etiology of tuberculosis, malignancy or autoimmune.

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laila Fakhriyatuz Zakiyah, MBBS; Phone Number: +6282139248828; Email: lailafz2007@gmail.com
• Study Contact Backup: Name: Gurmeet Singh, MD, PhD; Phone Number: +6281385158159; Email: gurmeetsingh10@yahoo.com

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • Respirology and Critical Illness Division, Department of Internal Medicine, Dr. Cipto Mangunkusumo General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hospitalized adult age 18 - 75 years old
• Willing to be involved in the research
• Undiagnosed transudative and exudative pleural effusion post-thoracentesis twice on right and left lung
• Patients can undergo medical thoracoscopy under local anesthesia, based on ATS and BTS guideline

Exclusion Criteria:

• Pregnant and breastfeeding women
• Patients in non-invasive ventilation and mechanical ventilator
• Transudative and exudative pleural effusion with etiology of chronic heart failure, chronic kidney disease, hepatocirrhosis with or without hepatic hydrothorax and hypoalbuminemia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: transudative pleural effusion; Subjects with undiagnosed transudative pleural effusion will undergo medical thoracoscopy as per studies protocols.	Procedure: Medical thoracoscopy; Medical thoracoscopy is a minimally invasive procedure to have access to pleura with combination of visual and medical instrument. The procedure is done with local and light anesthesia. Medical thoracoscopy plays role in basic diagnosis and therapeutic.; Other Names: pleuroscopy; Diagnostic test: CRP, D-dimer, ADA, ANA, C3 C4 complements, CA-125, Xpert MTB, LE cell, cytology and histopathology; CRP, D-dimer, ADA, ANA, C3 C4 complements, CA-125, Xpert MTB, LE cell, cytology and histopathology taken from specimen of effusion and smear; Drug: Lidocain, fentanyl and midazolam; local anesthetic: lidocaine 2%, fentanyl 100 mg and midazolam 2 mg
Other: exudative pleural effusion; Subjects with undiagnosed exudative pleural effusion will undergo medical thoracoscopy as per studies protocols.	Procedure: Medical thoracoscopy; Medical thoracoscopy is a minimally invasive procedure to have access to pleura with combination of visual and medical instrument. The procedure is done with local and light anesthesia. Medical thoracoscopy plays role in basic diagnosis and therapeutic.; Other Names: pleuroscopy; Diagnostic test: CRP, D-dimer, ADA, ANA, C3 C4 complements, CA-125, Xpert MTB, LE cell, cytology and histopathology; CRP, D-dimer, ADA, ANA, C3 C4 complements, CA-125, Xpert MTB, LE cell, cytology and histopathology taken from specimen of effusion and smear; Drug: Lidocain, fentanyl and midazolam; local anesthetic: lidocaine 2%, fentanyl 100 mg and midazolam 2 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical thoracoscopy diagnostic yield in undiagnosed transudative and exudative pleural effusion patients	Medical thoracoscopic diagnostic yield based on the diagnostic result of patients with undiagnosed transudative and exudative pleural effusion after maximum twice thoracocentesis with unknown etiology.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of undiagnosed transudative and exudative pleural effusion	The incidence measured by time in six months during subjects recruitment	2 weeks
Number of Incidence with etiology of infection, autoimmune and malignancy on undiagnosed transudative and exudative pleural effusion	Incidence number of infection, autoimmune and malignancy measured by the result of medical thoracoscopy diagnostic yield	2 weeks
Histopathology test result	Tissue taken from pleural cavity	2 weeks
Pattern of C-Reactive Protein (CRP)	CRP (mg/L)	2 weeks
Pattern of D-dimer	D-dimer (ng/ml)	2 weeks
Pattern of Adenosine Deaminase (ADA)	ADA (U/L)	2 weeks
Pattern of Anti Nuclear Antibody (ANA)	ANA (U)	2 weeks
Pattern of C3 C4 complements	C3 C4 complements (mg/dL)	2 weeks
Pattern of Carcinoma Antigen 125 (CA-125)	CA-125 (U/mL)	2 weeks
Result of Xpert MTB	MTB not detected or MTB detected rifampicin sensitive or rifampicin resistance	2 weeks
Pattern of Lupus Erythematosus cell (LE cell)	LE cell (%)	2 weeks
Result of cytology test	Cytology taken from pleural effusion and brushing	2 weeks

Collaborators and Investigators

• Sponsor: Indonesia University
• Collaborators: Singapore General Hospital
• Investigators: Principal Investigator: Gurmeet Singh, Faculty of Medicine, Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital

Publications and helpful links

General Publications

• Light RW. Clinical practice. Pleural effusion. N Engl J Med. 2002 Jun 20;346(25):1971-7. doi: 10.1056/NEJMcp010731. No abstract available.
• Rodriguez-Panadero F, Janssen JP, Astoul P. Thoracoscopy: general overview and place in the diagnosis and management of pleural effusion. Eur Respir J. 2006 Aug;28(2):409-22. doi: 10.1183/09031936.06.00013706. No abstract available.
• Ferreiro L, Toubes ME, San Jose ME, Suarez-Antelo J, Golpe A, Valdes L. Advances in pleural effusion diagnostics. Expert Rev Respir Med. 2020 Jan;14(1):51-66. doi: 10.1080/17476348.2020.1684266. Epub 2019 Nov 5.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 21, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Pleural Diseases; Pleural Effusion; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Immunologic Factors; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Fentanyl; Midazolam; Lidocaine; Complement System Proteins; Complement C4
• Other Study ID Numbers: 1111/UN2.RST/HKP.05.00/2022

Drug and device information, study documents

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