Study: NCT03873766

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Intrapleural Medications
Description: The IPFT group will receive a total of 5-6 doses of alteplase 10mg and DNase 5 mg twice daily x 3 days. delivered through a chest tube or small bore catheter into the pleural space. The doses will be given twice a day. If the first IPFT dose is given in the evening on the first day, they will only receive a total of 5 doses of the dual-agent IPFT (alteplase and DNase).

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Surgery
Description: The surgical arm will have either open surgery or a Video assisted Thoracoscopic Surgery (VATS) approach at the discretion of the surgeon

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Pleural Sampling
Description: Pleural fluid may be sampled by the responsible clinical service in the course of clinical care for patients with suspected pulmonary infection or by consulting service after identification of patient. Some patients will have a thoracentesis or tube drainage, and others will have no intervention at the time of referral for study eligibility review. Enrollment reflects real world clinical care and patients will be considered for enrollment regardless of sampling techniques or timing prior to evaluation

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Pleural Sampling
Description: Pleural fluid may be sampled by the responsible clinical service in the course of clinical care for patients with suspected pulmonary infection or by consulting service after identification of patient. Some patients will have a thoracentesis or tube drainage, and others will have no intervention at the time of referral for study eligibility review. Enrollment reflects real world clinical care and patients will be considered for enrollment regardless of sampling techniques or timing prior to evaluation

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Pleural fluid drainage
Description: All patients in the study must have tube thoracostomy for drainage of the pleural space. This may have been done by the clinically responsible team or by the study team. Physicians may select chest tubes of any type, but the minimum size is 14 French. For patency, chest tubes 14-20 French should be kept at negative 20 suction and flushed daily. Large bore chest tubes (\>20French) may be kept at negative 20 suction at the discretion of the physician managing the chest tube and do not require daily flushing. Supportive care will follow Institutional Guidelines.

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Pleural fluid drainage
Description: All patients in the study must have tube thoracostomy for drainage of the pleural space. This may have been done by the clinically responsible team or by the study team. Physicians may select chest tubes of any type, but the minimum size is 14 French. For patency, chest tubes 14-20 French should be kept at negative 20 suction and flushed daily. Large bore chest tubes (\>20French) may be kept at negative 20 suction at the discretion of the physician managing the chest tube and do not require daily flushing. Supportive care will follow Institutional Guidelines.

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Protocol Image #1
Description: Once the chest tube is placed, imaging is obtained within 24-48 hours to assess the fluid drainage. The choice of image, either Chest X-ray or CT Chest, is up to the discretion of the treating physician. Based on the imaging, patients will be separated into 2 groups:~A: Complete drainage/re-expansion of the lung: If there is complete drainage of the pleural fluid collection and lung re-expansion based on image #1, patients will follow usual clinical care without randomization and be observed until discharge. Patients will remain in the study and their data will be collected.~B: Incomplete drainage/incomplete lung re-expansion: For those patients that have incomplete drainage of the pleural fluid collection on image #1 and/or the lung does not re-expand.

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Protocol Image #1
Description: Once the chest tube is placed, imaging is obtained within 24-48 hours to assess the fluid drainage. The choice of image, either Chest X-ray or CT Chest, is up to the discretion of the treating physician. Based on the imaging, patients will be separated into 2 groups:~A: Complete drainage/re-expansion of the lung: If there is complete drainage of the pleural fluid collection and lung re-expansion based on image #1, patients will follow usual clinical care without randomization and be observed until discharge. Patients will remain in the study and their data will be collected.~B: Incomplete drainage/incomplete lung re-expansion: For those patients that have incomplete drainage of the pleural fluid collection on image #1 and/or the lung does not re-expand.

Intervention type: OTHER
Group type: ACTIVE_COMPARATOR
Intervention: Surgical Consultation
Description: A thoracic surgery consultation will be obtained on all patients with incomplete drainage and/or the lung does not re-expand, to determine surgical candidacy. Those patients that the surgical team deem unsafe for surgery will receive clinically appropriate guideline centered, non-surgical, care. These patients will not be randomized but they will remain in the study and their data will be collected. Criteria deeming patients unfit for surgery include, but are not limited to: inability to tolerate single lung ventilation, severe chronic obstructive pulmonary disease (COPD), and risk of surgery prohibitive. Patients not excluded from surgery will be randomized.

Intervention type: OTHER
Group type: ACTIVE_COMPARATOR
Intervention: Surgical Consultation
Description: A thoracic surgery consultation will be obtained on all patients with incomplete drainage and/or the lung does not re-expand, to determine surgical candidacy. Those patients that the surgical team deem unsafe for surgery will receive clinically appropriate guideline centered, non-surgical, care. These patients will not be randomized but they will remain in the study and their data will be collected. Criteria deeming patients unfit for surgery include, but are not limited to: inability to tolerate single lung ventilation, severe chronic obstructive pulmonary disease (COPD), and risk of surgery prohibitive. Patients not excluded from surgery will be randomized.

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Protocol Image #2: Chest X-ray PA/Lateral
Description: The morning after intervention completion (surgery or last dose of IPFT), a chest X-ray PA/lateral will be obtained (protocol image #2). Based on Image #2 the patient will be categorized into one of three groups: satisfactory improvement of pleural fluid collection, unsatisfactory improvement in pleural fluid collection on imaging, or treatment failures.

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Protocol Image #2: Chest X-ray PA/Lateral
Description: The morning after intervention completion (surgery or last dose of IPFT), a chest X-ray PA/lateral will be obtained (protocol image #2). Based on Image #2 the patient will be categorized into one of three groups: satisfactory improvement of pleural fluid collection, unsatisfactory improvement in pleural fluid collection on imaging, or treatment failures.

Intervention type: BEHAVIORAL
Group type: ACTIVE_COMPARATOR
Intervention: Quality of Life
Description: Quality of life will be measured at 30 day and 90 day and 1 year clinical follow-up using the SF-36 quality of life survey and return to work questionnaires

Intervention type: BEHAVIORAL
Group type: ACTIVE_COMPARATOR
Intervention: Quality of Life
Description: Quality of life will be measured at 30 day and 90 day and 1 year clinical follow-up using the SF-36 quality of life survey and return to work questionnaires