Impact of Pleural Manometry on Chest Discomfort After Therapeutic Thoracentesis

Study Overview
=================
Brief Summary
-----------------
This randomized controlled trial attempts to determine whether the measurement of pleural pressures during therapeutic thoracentesis affects the development of chest discomfort after the procedure. During thoracentesis, pleural fluid is drained from the pleural space, resulting in lung expansion. In some cases, the lung is not completely re-expandable, in which case continued drainage results in the development of negative pleural pressures and chest discomfort. Negative pleural pressures may also result in other complications such as re-expansion pulmonary edema and pneumothorax. The identification of negative pleural pressures via manometry during the procedure may lead to a reduction in the complication rate.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To study the impact of pleural manometry on the development of chest discomfort during therapeutic thoracentesis compared to conventional symptom-guided thoracentesis. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo manometry-guided therapeutic thoracentesis. ARM II: Patients undergo symptom-guided thoracentesis.

Official Title
-----------------
Manometry- Versus Symptom-Guided Large Volume Thoracentesis: a Randomized Controlled Study

Conditions
-----------------
Pleural Effusion

Intervention / Treatment
-----------------
* Other: Manometry-guided thoracentesis
* Other: Symptom-guided thoracentesis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Referral to pulmonary or interventional radiology services for large-volume thoracentesis Presence of a symptomatic moderate or large free-flowing pleural effusion on the basis of: Chest radiograph: effusion filling >= 1/3 the hemithorax, OR Computed tomography (CT)-scan: maximum anteroposterior (AP) depth of the effusion >= 1/3 of the AP dimension on the axial image superior to the hemidiaphragm, including atelectatic lung completely surrounded by effusion, OR Ultrasound: effusion spanning at least three rib spaces with depth of >= 3 cm Exclusion Criteria: Inability to provide informed consent Study subject has any disease or condition that interferes with safe completion of the study including: Coagulopathy, with criteria left at the discretion of the operator Hemodynamic instability with systolic blood pressure < 90 mmHg or heart rate > 120 beats/min, unless deemed to be stable with these values by the attending physicians Pleural effusion is smaller than expected on bedside pre-procedure ultrasound Referral is for diagnostic thoracentesis only Manometry felt to be clinically indicated Inability to assume or maintain a seated position for the procedure Presence of multiple loculations on bedside pre-procedure ultrasound

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: Manometry-guided thoracentesis<br>Intervention Group - Patients undergo fine needle- aspiration, called therapeutic thoracentesis, to drain fluid accumulated around the lung. Unlike Arm II, the intervention group will have their pleural pressure monitored during the procedure. | Other: Manometry-guided thoracentesis<br>* Arm I will undergo a standard of care therapeutic thoracentesis procedure, and in addition include pleural pressure monitoring (via an FDA-approved digital manometer) which is also standard of care but left at the discretion of physicians as per expert recommendations. In this group, the procedure will be stopped when the patient develops symptoms or when all the fluid has been removed, and will also be stopped if the pressure begins to fall quickly in the fluid collection.<br>Other: Symptom-guided thoracentesis<br>* Arm II will undergo a standard of care therapeutic thoracentesis procedure. In this group, the procedure but will be stopped when the patient develops symptoms or when all the fluid has been removed.<br>|
| Active Comparator: Arm II: Symptom-guided thoracentesis<br>Comparison Group - Patients undergo symptom-guided thoracentesis, the current standard-of-care is to drain fluid until 1) it is all gone or 2) a symptom occurs that indicates the lung may take longer to fully re-expand and drainage should be stopped. | Other: Symptom-guided thoracentesis<br>* Arm II will undergo a standard of care therapeutic thoracentesis procedure. In this group, the procedure but will be stopped when the patient develops symptoms or when all the fluid has been removed.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in post-procedure chest discomfort scores between control (symptom-guided) and intervention (manometry-guided) groups | As measured in millimeters along a 10 cm Visual Analog Scale (VAS). The estimated minimal clinically important difference is 15 mm. Descriptive statistics including means, standard deviations, and ranges will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention versus (vs) control, will be made using the t-test or Wilcoxon Rank Sum test. Mixed model will be employed to assess the trend of pain score measured across pre-, intra-, and post-procedure. | one-time assessment, 5 minutes after thoracentesis catheter is removed (on day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in chest discomfort scores from pre-procedure to post-procedure. | As measured in millimeters along a 10 cm Visual Analog Scale (VAS). Descriptive statistics including means, standard deviations, and ranges will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention versus (vs) control, will be made using the t-test or Wilcoxon Rank Sum test. Mixed model will be employed to assess the trend of pain score measured across pre-, intra-, and post-procedure. | From 1 minute pre-procedure to 5 minutes after thoracentesis catheter is removed (on day 1) | 
| Incidence of complete lung re-expansion, as assessed by post-procedure chest radiograph | Descriptive statistics including percentages and frequencies will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention vs control, will be made using the Chi-square test. | 20 minutes after thoracentesis catheter is removed (on day 1) | 
| Duration of procedure | Measured in seconds, assessed from the time the thoracentesis catheter is introduced to the time the catheter is removed. Descriptive statistics including means, standard deviations, and ranges will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention vs control, will be made using the t-test or Wilcoxon Rank Sum test. | during the procedure, on day 1, intraoperative | 
| Change in subjective report of dyspnea | Assessed in millimeters along a 10 cm Visual Analog Scale (VAS), from pre-procedure (baseline) to 5 minutes after completion of the procedure. Descriptive statistics including means, standard deviations, and ranges will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention vs control, will be made using either the t-test or Wilcoxon Rank Sum test. | From 1 minute pre-procedure to 5 minutes after thoracentesis catheter is removed (on day 1) | 
| Incidence of clinically-significant re-expansion pulmonary edema | Assessed as present if immediate post-procedure chest radiograph demonstrates new pulmonary edema per radiologist interpretation when compared to pre-procedure radiograph in the hemithorax that underwent thoracentesis, and subject has post-procedure new-onset or worsened hypoxic respiratory failure. Descriptive statistics including percentages and frequencies will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention vs control, will be made using the Chi-square test. | 20 minutes after thoracentesis catheter is removed (on day 1) | 
| Incidence of pneumothorax | Assessed as either present or absent on the immediate post-procedure chest radiograph per radiologist interpretation. Descriptive statistics including percentages and frequencies will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention vs control, will be made using the Chi-square test. | 20 minutes after thoracentesis catheter is removed (on day 1) | 
| Incidence of radiographically-apparent re-expansion pulmonary edema | Assessed as present if immediate post-procedure chest radiograph demonstrates new pulmonary edema per radiologist interpretation when compared to pre-procedure radiograph in the hemithorax that underwent thoracentesis. Descriptive statistics including percentages and frequencies will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention vs control, will be made using the Chi-square test | 20 minutes after thoracentesis catheter is removed (on day 1) | 
| Volume of pleural fluid removed by the thoracentesis procedure | Measured in milliliters. Descriptive statistics including means, standard deviations, and ranges will be presented. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made. If necessary, data will be transformed using Box-Cox power transformation. Comparisons between groups, i.e. intervention vs control, will be made using the t-test or Wilcoxon Rank Sum test. | immediately after the thoracentesis catheter is removed, on day 1 |