Treatment of Complicated Parapneumonic Effusion With Fibrinolytic Therapy Versus VATs Decortication

Study Overview
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Brief Summary
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This study aims to standardize the treatment of pleural space (parapneumonic) infections by comparing the difference in outcomes between 2 methods of treatment: early VATS (Video Assisted Thorascopic Surgery) decortication versus fibrinolytic therapy. During treatment, the patient's coagulopathy status will also be evaluated.

Detailed Description
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The treatment of parapneumonic infections (infection in the pleural space) at the Denver Health Medical Center is not standardized, and timing for advanced interventions such as fibrinolytic therapy or surgical decortication remain unclear. The definitive treatment strategy in these patients may be sub-optimal, and lead to prolonged hospitalization and morbidity. This is concerning as the mortality rate of community acquired pneumonia triples in the presence of a parapneumonic process (5-15%) and can reach over 25% if it becomes bilateral(1). Prompt recognition of pleural space infections is essential for reducing morbidity and mortality. This is attributable to the progression of the disease from a simple fluid collection amenable to pleural space drainage, to necrotizing empyema requiring thoracotomy decortication and open drainage. The keys to management of parapneumonic effusions are early diagnosis, appropriate therapeutic intervention, and recognition of failure of conservative management. The investigators propose that a standardized pathway for identifying and treating parapneumonic effusions will be an important quality improvement. A key gap in the literature remains if patients with parapneumonic infections that cannot be drained with a chest tube should undergo a trial in intrapleural fibrinolytic therapy, or if they should go directly to video assisted thoracic surgery (VATS) for decortication of all infectious material.

Official Title
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Early Intervention for Complicated Parapneumonic Effusion: Randomized Controlled Trial for Fibrinolytic Therapy Versus VATs Decortication

Conditions
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Parapneumonic Effusion, Empyema, Pleural, Coagulopathy

Intervention / Treatment
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* Procedure: VATS Decortication
* Drug: Fibrinolytic Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old and older Admitted with pleural effusion that undergoes thoracentesis by medical/pulmonary service Pleural fluid pH <7.3 SICU placed chest tube Subsequent transfer to SICU Exclusion Criteria: Existing malignancy Malignant cells from initial pleural fluid sample End stage liver disease (Child's B or greater) Coagulopathy Unable to tolerate surgical procedure Frank purulent drainage (needs OR regardless) Recent surgery of abdomen or thorax precluding the use of tPA Baseline neurologic impairment requiring a proxy for consent

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective Randomized Clinical Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Operative VATS decortication<br>Operative group that will undergo early VATS decortication of complicated parapneumonic effusion/empyema | Procedure: VATS Decortication<br>* Surgical procedure to unroof all located collections of the pleural space through a chest wall incision<br>|
| Active Comparator: Non-operative Fibrinolytic Therapy<br>Non-operative group that will undergo instillation of the drugs DNAse and tPA (tissue plasminogen activator) together i.e. 5mg DNAse and 10mg tPA twice a day for up to six doses, through chest tube as treatment of the patient's complicated parapneumonic effusion/empyema. Fibrinolytic therapy = DNAse + tPA; these medications are not mutually exclusive. | Drug: Fibrinolytic Therapy<br>* Instillation of DNAse and tPA together through patient's chest tube already in placed to break down complex fluid collection in the pleural space. DNAse and tPA are are administered together only i.e. are not mutually exclusive.<br>* Other names: DNAse / tPA combination therapy.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Length of Stay | How long the patient remains admitted in the hospital during their index hospitalization | From patient's admission to hospital to their discharge, (excluding extended stay due to social work reasons) up to 28 days or discharge, which ever comes first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU Free Days | Admission days during index hospitalization that are of a lower acuity of care than intensive care | From admission to discharge, or for 28 days, whichever comes first. | 
| Chest Tube Days | Days with chest tube in place after intervention | From admission to discharge, or for 28 days, whichever comes first. | 
| Cost of Admission and Treatment | Cost of care for the patient after their intervention | From admission to discharge, or for 28 days, whichever comes first. | 
| Pain Score | What the patient's level of pain is from 0 to 10; zero being no pain, 10 being the worst pain imaginable. score is categorical 0,1,2,3,4,5,6,7,8,9 or 10. | From admission to discharge, or for 28 days, whichever comes first. | 
| Chest Tube Drainage | The amount and character of the drainage from the chest tube after intervention | From admission to discharge, or for 28 days, whichever comes first. | 
| Incentive Spirometry | To what volume the patient can inspire using an incentive spirometer | Everyday for 5 days post study intervention, from admission to discharge, or for 28 days, whichever comes first. | 
| Supplemental Oxygen Days | The amount of time the patient needs to warn off any supplemental oxygen | From admission to discharge, or for 28 days, whichever comes first. | 
| Fever Days | The amount of days it takes to resolve fever (temp >100.4) | From admission to discharge, or for 28 days, whichever comes first. | 
| Days of Antibiotics | The number of days antibiotics are required after intervention | From admission to discharge, or for 28 days, whichever comes first. | 
| Elevated White Blood Count Days | The amount of days it takes to resolve a leukocytosis | From admission to discharge, or for 28 days, whichever comes first. | 
| Changed in Coagulopathic Status | Changes in laboratory TEG values after intervention | From admission to discharge, or for 28 days, whichever comes first. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VATS Decortication, Surgical Pleural Decortication, Fibrinolytic Therapy, Pneumonia, Thoracostomy