A Randomised Study Evaluating Diagnostics of Pleural Effusion Among Patients Suspect of Cancer.

Local Anesthetic Thoracoscopy Versus Ultrasound Guided Pleural Biopsies and Repeat Thoracocentesis in Pleural Effusion After Inconclusive Initial Thoracentesis: a Randomized Study

Pleural fluid can be caused by cancer. Patients with repeated presentation of pleural fluid where initial diagnostic tests have been inconclusive are the focus of this trial. In this clinical trial patients are randomized into two groups and the efficacy of local anesthetic thoracoscopy (LAT) is compared to an ultrasound guided biopsy of the outer lining of the lung. The aim is not only the diagnostic yield in diagnosing cancer, but also the procedures ability to diagnose specific cancer mutations and immune system markings.

Methods and objectives:

Patients with reoccuring one-sided pleural fluid, with a marked clinical risk of cancer based on findings in medical work-up, radiological scans, biochemistry and medical history and who are undiagnosed upon initial pleural fluid analysis are the target patients of the trial. Patients are randomized into two groups to have undertaken either pleural biopsy at the optimal site for a repeat thoracentesis or LAT. Thus diagnostic yield for both fluid analysis and biopsy analysis will be compared to tissue samples taken with LAT.

We hypothesize that LAT is superior both to pleural biopsy and repeat thoracentesis in providing diagnostic clarification and providing sufficient basis for treatment without further procedures resulting in less time consumption, cost and discomfort for the patient.

Study Overview

• Status: Terminated
• Conditions: Pleural Effusion, Malignant; Pleural Effusion; Pleura; Exudate
• Intervention / Treatment: Procedure: US-guided pleural biopsy; Procedure: Local anesthetic thoracoscopy

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Næstved, Denmark, 4700
    • Næstved Hospital
  • Roskilde, Denmark, 4000
    • University Hospital Zealand, Roskilde

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older patients with single previous thoracentesis of a unilateral pleural exudate according to Lights criteria without malignant cells.
• Lights Criteria:

Pleural fluid protein/serum protein ratio greater than 0.5 pleural fluid LDH/serum LDH ratio greater than 0.6 Pleural fluid LDH greater than two-thirds the upper limits of the Laboratorys normal Serum LDH

• Contrast enhanced CT of the Chest and abdomen performed
• Clinical suspicion of cancer such as, but not limited to, weight loss, malaise, anemia
• Pet-CT results or former cancer diagnosis Informed consent

Exclusion Criteria:

• bilateral pleural effusions
• known cause of pleural effusion
• likely non-malignant course of a unilateral pleura effusion such as (but not restricted to) pneumonia, trauma, pleuritis, heart failure
• any contraindication to the study procedures

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
Active Comparator: US-guided pleural biopsy and thoracentesis; Pleural biopsy: Using ultrasound the optimal point of entry for thoracentesis is located, and local anesthesia is obtained. The area is wiped with disinfectant and a skin incision is made with a pointed scalpel. Six US-guided biopsies of 1x2 millimetres are taken from the parietal pleura using closed needle biopsies (Quick-core Biopsy Needle 18G, COOK Medical, Bloomington, Indiana, USA or Bard Max Core Biopsy Needle 18G, Tempe, Arizona, USA). Afterward, a thoracentesis is performed in the same incision as used by the pleural biopsy. A pigtail catheter is inserted and fastened and connected to a sealed bag and fluid is aspirated and sent to relevant analysis.	Procedure: US-guided pleural biopsy; In local anesthesia, a closed needle biopsy is performed Ultrasound guided of the parietal pleura at the place of deepest fluid recess in the intrathoracic space. A pigtail catheter French 7-16 is placed afterwards for fluid drainage.
Experimental: LAT and thoracentesis; Local anesthetic thoracoscopy: Pre-procedure a pleural pigtail catheter is inserted and pleural fluid is removed. The catheters one-way valve is opened and the patient takes several breaths thereby creating a pneumothorax prior to procedure start. The patient is sedated with midazolam and morphine. Midaxillary access through intercostal space 4-7 is achieved in local anesthesia and via a skin incision a trocar is placed for access to the thoracic space. A semi-rigid thoracoscope (model LTF 160; Olympus, Tokyo, Japan) is inserted via the trocar and the pleural cavity is inspected after removal of residual effusion whereof at least 40ml is sent to cytology. Pleural parietal biopsies are taken under direct visual guidance. The recommended number of biopsies is 10-15. If no abnormalities were seen, random biopsies are taken. After relevant biopsies are taken the instruments are removed the pigtail catheter stays inserted to allow for removal of air and expansion of the lung.	Procedure: Local anesthetic thoracoscopy; Procedure to obtain histological biopsies of the parietal pleura on awake, fastening patients.; Other Names: medical thoracoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-guiding pleural workup to provide and plan treatment for the cause of the pleura exudate, local anesthetic thoracoscopy vs 2. thoracentesis	Difference in incidence of treatment-guiding diagnostic workup in local anesthetic thoracoscopy versus 2nd thoracentesis	26 weeks
Incidence of treatment-guiding pleural workup to provide and plan treatment for the cause of the pleura exudate. Local anesthetic thoracoscopy vs US-guided pleural biopsy.	Difference in incidence of treatment-guiding diagnostic workup in local anesthetic thoracoscopy versus US-guided pleural biopsy prior to 2nd thoracentesis	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of achieving pleural immunohistochemistry, mutations, oncodrivers, culture and biochemistry.		26 weeks
Incidence of completed procedures		1 week
Time from randomization to conclusive, treatment-guiding diagnoses		26 weeks
Time from start of consultation with medical staff until end of consultation with medical staff on the day of the procedure		Day of procedure/intervention
Time from procedure start to patient leaving the procedure room and leaving the recovery room		Day of procedure/intervention
Adverse event; complication to procedure: mortality	Evaluated on day of procedure, 7 days and 30 days. The 2 last are performed via telephone call to the patient and informations gathering in the electronic patient file system	30 days.
Adverse event; complication to procedure: pneumothorax	Evaluated on day of procedure, 7 days and 30 days. The 2 last are performed via telephone call to the patient and informations gathering in the electronic patient file system	30 days.
Adverse event; complication to procedure: haemoptysis	Evaluated on day of procedure, 7 days and 30 days. The 2 last are performed via telephone call to the patient and informations gathering in the electronic patient file system	30 days.
Adverse event; complication to procedure: infection	Evaluated on day of procedure, 7 days and 30 days. The 2 last are performed via telephone call to the patient and informations gathering in the electronic patient file system	30 days.
Adverse event; complication to procedure: hospital admission	Evaluated on day of procedure, 7 days and 30 days. The 2 last are performed via telephone call to the patient and informations gathering in the electronic patient file system	30 days.
Total volume of pleural fluid removed	In mililiter (ml)	Day of procedure
Patient reported discomfort reported via ESAS	ESAS - Edmonton Symptom Assesment System, Danish Version 2008	Day of procedure pre- and post-procedure and 1 week followup
Patient reported discomfort reported via EQ-5D-5L	Denmark (Danish) © 2009 EuroQol Group EQ-5D™	Day of procedure pre- and post-proceudre and 1 week followup
Willingness to repeat procedure	5 Point Likert Scale, 1 not likely to repeat, 5 most likely to repeat	After procedure performed - within 30 minutes and 1 week after proceudre
Cough	Visual analogue scale 1-10. 1 Being no cough, 10 being extreme cough	Pre-procedure, 1 week post procedure.

Collaborators and Investigators

• Sponsor: Naestved Hospital
• Investigators: Study Chair: Uffe Bødtger, MD ph.d., Næstved

Publications and helpful links

General Publications

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• Hooper C, Lee YC, Maskell N; BTS Pleural Guideline Group. Investigation of a unilateral pleural effusion in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010 Aug;65 Suppl 2:ii4-17. doi: 10.1136/thx.2010.136978. No abstract available.
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• Porcel JM, Esquerda A, Vives M, Bielsa S. Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. Arch Bronconeumol. 2014 May;50(5):161-5. doi: 10.1016/j.arbres.2013.11.007. Epub 2013 Dec 20. English, Spanish.
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• Hallifax RJ, Corcoran JP, Ahmed A, Nagendran M, Rostom H, Hassan N, Maruthappu M, Psallidas I, Manuel A, Gleeson FV, Rahman NM. Physician-based ultrasound-guided biopsy for diagnosing pleural disease. Chest. 2014 Oct;146(4):1001-1006. doi: 10.1378/chest.14-0299.
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Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Actual): September 24, 2020
• Study Completion (Actual): September 24, 2020

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 15, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2020
• Last Update Submitted That Met QC Criteria: September 24, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Pleural effusion; Malignant Pleural effusion; Pleura diagnostics; US-guided pleural biopsy; Local anesthetic thoracoscopy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local
• Other Study ID Numbers: SJ-790

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