Ultrasound-guided Biopsy of the Pleura as a Supplement to Extraction of Fluid in Patients With One-sided Fluid in the Pleura

Ultrasound-guided Pleural Biopsy as a Supplement to Thoracentesis: A Randomised Study

The research group will investigate the diagnostic effect of early introduction of ultrasound guided pleural biopsy in the work-up of patients with one-sided pleural effusion, suspected of malignant pleural effusion.

Study Overview

• Status: Terminated
• Conditions: Malignant Pleural Effusion; Exudative Pleural Effusion
• Intervention / Treatment: Procedure: Thoracentesis; Procedure: ultrasound-guided pleural biopsy

Detailed Description

Patients with unilateral pleural effusion with high protein content (exudative pleural effusion) are likely to have malignant pleural effusion. In the Danish guidelines, patient undergo two thoracentesis before more invasive procedures, due to the relatively low incidens of pleural TB and mesothelioma. The aim of the research group is to investigate the effect of early introduction of ultrasound-guided pleural biopsy taken at the optimal sport for thoracentesis. The research group will randomise half of our patients with unilateral pleural exudate to up-front ultrasound-guided biopsy and the other half usual care eg. a second thoracentesis, to see if there is a benefit of early pleural biopsy in the work-up of patients with unilateral pleural effusion, suspected of malignant pleural effusion.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Region Sjælland
    • Næstved, Region Sjælland, Denmark, 4700
      • Næstved Sygehus, department of pulmonary medicine
  • Zealand
    • Roskilde, Zealand, Denmark, 4000
      • Zealand University Hospital, Roskilde, Department of Pulmonary medicine

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.
• Patients with a previous thoracentesis of a unilateral exudative pleural effusion according to Light's criteria (1) without malignant cells.
• CT thorax or PET-CT with contrast performed.
• Clinical suspicion of cancer such as (but not limited to) weight loss or PET-CT results or former cancer diagnosis.
• Patients must be able to give informed consent.

Exclusion Criteria:

• Bilateral pleural effusions.
• Known cause of pleural effusions.
• Life expectancy <3 months.
• Inability to understand written or spoken Danish.

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: Ultrasound-guided thoracentesis; Ultrasound guided thoracentesis	Procedure: Thoracentesis; The optimal point of entry (the largest distance between parietal and visceral pleura) is identified using ultrasound. This is usually on the lower, dorsal side of the chest. Local anesthesia is obtained with 10 mL of 2% lidocaine with adrenalin injected in cutis, subcutis, muscle and pleura. Before removing the syringe, aspiration of pleural fluid confirms the relevance of the chosen site. The area is wiped with disinfectant and a millimeter skin incision is made with a pointed scalpel. A 7 French (or up to 16 French, to the choice of the clinician) pigtail catheter is inserted and connected to sealed bag. Fluid is aspirated via a 3-way valve, and transferred to relevant bottles for culture, analysis of albumin and LDH, protein, and for cytology.
Experimental: Ultrasound-guided pleural biopsy and thoracentesis; Ultrasound-guided biopsy of the parietal pleura is taken through the same incision as the optimal site for thoracentesis and immediately prior to ultrasound-guided thoracentesis	Procedure: Thoracentesis; The optimal point of entry (the largest distance between parietal and visceral pleura) is identified using ultrasound. This is usually on the lower, dorsal side of the chest. Local anesthesia is obtained with 10 mL of 2% lidocaine with adrenalin injected in cutis, subcutis, muscle and pleura. Before removing the syringe, aspiration of pleural fluid confirms the relevance of the chosen site. The area is wiped with disinfectant and a millimeter skin incision is made with a pointed scalpel. A 7 French (or up to 16 French, to the choice of the clinician) pigtail catheter is inserted and connected to sealed bag. Fluid is aspirated via a 3-way valve, and transferred to relevant bottles for culture, analysis of albumin and LDH, protein, and for cytology.; Procedure: ultrasound-guided pleural biopsy; Using ultrasound the optimal point of entry for thoracentesis is located. Local anesthesia is obtained with 10 mL of 2% lidocaine with adrenalin injected in cutis, subcutis, muscle and pleura. Before removing the syringe, aspiration of pleural fluid confirms the relevance of the chosen site . Again, the area is wiped with disinfectant and a millimeter small skin incision is made with a pointed scalpel. Six US-guided biopsies of 1.2 millimetres using closed needle biopsies (Quick-core Biopsy Needle 18G, COOK Medical, Bloomington, Indiana, USA or Bard Max Core needle 18G, Temple, Arizona, USA). ) are taken from the parietal pleura. Thoracentesis is performed as described above using the same incision as the pleural biopsy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of cases with conclusive pleural workup to provide and plan treatment in patients diagnosed with malignant pleural effusion.	Our primary endpoint includes both patients who will receive palliative care and patients who will receive active treatment. For patients receiving palliative care, the presence of malignant cells is sufficient. However, for patients receiving active treatment, the primary endpoint is defined as a definite and treatment-guiding pathological result (immunohistochemistry, mutations, oncodrivers, culture and biochemistry) as decided by a multidisciplinary team conference.	26 weeks post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of cases achieving pleural immunohistochemistry, mutations, oncodrivers and culture.		26 weeks post randomization
Difference in diagnostic yield between Arm A and Arm B, including subgroup analysis of MPE.		26 weeks post randomization
Sensitivity of ultrasound-guided closed needle biopsy of parietal pleura for diagnosing malignancy and all causes of PE.		26 weeks post randomization
Time from inclusion to conclusive, treatment-guiding diagnoses in patients with MPE.		26 weeks post randomization
The negative likelihood ratio of additional ultrasound-guided closed needle biopsy of parietal pleura in aspect of MPE.		26 weeks post randomization
Proportion of true non-malignant PE at end of follow-up.		26 weeks post randomization
Complications to pleural procedures	mortality, pneumothorax, haemoptysis, local bleeding, infections and hospital admissions	Day 1 (1 hour after the end of procedure), 7 days and 30 days post-procedure
Mean volume pleural fluid drained during thoracentesis	measured in mL	Day 1 within 30 minutes after the end of procedure
Patient reported discomfort and health	measured by 5Q-5D-5L (2009 EuroQol Group EQ-5D™ Danish version).	Day 1within 30 minutes after the end of procedure and 7 days post-procedure
Patient reported discomfort and health	Measured by Edmonton Symptom Assessment System (ESAS), scale 1-10, 0 being no symptoms, 10 being the worse symptoms	Day 1 (immediately before procedure and within 30 minutes after the end of procedure) and 7 days post-procedure
Patient reported cough	VAS score (visual analogue scale) for cough, 0-10, 0 being no cough, 10 being the worse cough	Day 1(immediately before procedure and within 30 minutes after the end of procedure) and 7 days post-procedure
Pain during procedure	Measured by VAS score (visual analogue scale) for pain, 0-10, 0 being no pain, 10 being the worse pain	Day 1(within 30 minutes after the end of procedure)
Willingness to repeat the procedure	Measured by 5-point Likert scale,scale 1-5, 1 being definitely willing to have the procedure again, 5 being definitely not willing to have the procedure performed again	day og procedure (within 30 minutes after the end of procedure) and 1 week post-procedure
Change in patient reported discomfort	iMeasured by Edmonton Symptom Assessment System (ESAS) and VAS score (visual analogue scale) for cough	Day 1 within 30 minutes after the end of procedure
Changes in patient reported discomfort and health	Measured by Edmonton Symptom Assessment System (ESAS) and VAS score (visual analogue scale) for cough and health measured by 5Q-5D-5L (2009 EuroQol Group EQ-5D™ Danish version).	7 days post-procedure
Number of thoracenteses in these 7 days besides the study procedure.		7 days post-procedure

Collaborators and Investigators

• Sponsor: Naestved Hospital
• Investigators: Principal Investigator: Uffe Bødtger, MD, PhD,, Department of Respiratory Medicine; Naestved Hospital, Denmark

Publications and helpful links

General Publications

• Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med. 1972 Oct;77(4):507-13. doi: 10.7326/0003-4819-77-4-507. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Actual): September 23, 2020
• Study Completion (Actual): September 23, 2020

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: January 19, 2020
• First Posted (Actual): January 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• 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
• Other Study ID Numbers: SJ-787

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