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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pleural Effusion, Malignant, Pleural Effusion, Pleura; Exudate

Intervention / Treatment
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* Procedure: Local anesthetic thoracoscopy
* Procedure: US-guided pleural biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: US-guided pleural biopsy and thoracentesis<br>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<br>* 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.<br>|
| Experimental: LAT and thoracentesis<br>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<br>* Procedure to obtain histological biopsies of the parietal pleura on awake, fastening patients.<br>* Other names: medical thoracoscopy;|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pleural effusion, Malignant Pleural effusion, Pleura diagnostics, US-guided pleural biopsy, Local anesthetic thoracoscopy