Management of Pleural Space Infections

NCT ID: NCT03873766

Last Updated: 2022-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-01

Study Completion Date

2022-03-11

Brief Summary

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Currently, there is no high-quality evidence comparing the clinical outcomes and cost effectiveness of surgical drainage combined with antibiotics versus dual-agent intrapleural fibrinolytic therapy (IPFT) catheter drainage of pleural space infections with concomitant antibiotic therapy. The absence of comparative data is a challenge for surgical and medical services in clinical decision-making for this common and morbid condition.

This is a pilot study comparing surgical drainage of the pleural space in complex pleural effusions to bedside chest tube drainage using dual agent IPFT with the intent to inform on study algorithm and endpoint performance in anticipation of a multi-institutional randomized clinical trial.

Detailed Description

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Currently, there is no high-quality evidence comparing the clinical outcomes and cost effectiveness of surgical drainage combined with antibiotics versus dual-agent intrapleural fibrinolytic therapy (IPFT) catheter drainage of pleural space infections with concomitant antibiotic therapy. The absence of comparative data is a challenge for surgical and medical services in clinical decision-making for this common and morbid condition.

This is a pilot study comparing surgical drainage of the pleural space in complex pleural effusions to bedside chest tube drainage using dual agent IPFT with the intent to inform on study algorithm and endpoint performance in anticipation of a multi-institutional randomized clinical trial.

Patient's with complex pleural space infections identified at the institution that meet inclusion criteria will be randomized to receive either IPFT or surgical debridement after a surgery consultation is obtained. Patients randomized to the IPFT study arm will receive a total of 5-6 doses of alteplase 10mg and DNase 5 mg BID 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). The surgical arm will have either open surgery of a VATS approach at the discretion of the surgeon.

IPFT (alteplase and DNase) is not an investigational agent. It is used in standard of care practice for the treatment of complex pleural space infections. The investigators seek to compare dual-agent IPFT (alteplase and DNase) to surgery in this study. As such, the IPFT agents will be ordered from pharmacy through the electronic medical record (EMR) as in normal practice and there is not a study drug.

After drainage, patients will be followed with protocol images to assess the drainage of their pleural space. If there is satisfactory improvement in the pleural fluid collection on imaging chest tube or small bore catheter will be removed per protocol in both study arms. Chest tube removal protocol is based on fluid character and measured output.

Conditions

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Empyema, Pleural Parapneumonic Effusion

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients will be randomized to either IPFT or surgery for treatment of their complex pleural space infection
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intrapleural fibrinolytic therapy (IPFT)

* Procedure/Surgery: Pleural Sampling
* Procedure/Surgery: Pleural fluid drainage
* Protocol Image #1: After chest tube is placed, imaging is obtained within 24-48 hours to assess the fluid drainage.
* Other: Surgical Consultation
* Intrapleural Medications (IPFT): 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.
* Protocol Image #2: Chest X-ray PA/Lateral: The morning after intervention completion, a chest X-ray PA/lateral will be obtained
* Quality of Life: 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

Group Type ACTIVE_COMPARATOR

Intrapleural Medications

Intervention Type DRUG

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).

Pleural Sampling

Intervention Type PROCEDURE

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

Pleural fluid drainage

Intervention Type PROCEDURE

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.

Protocol Image #1

Intervention Type RADIATION

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.

Surgical Consultation

Intervention Type OTHER

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.

Protocol Image #2: Chest X-ray PA/Lateral

Intervention Type RADIATION

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.

Quality of Life

Intervention Type BEHAVIORAL

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

Surgery

* Procedure/Surgery: Pleural Sampling
* Procedure/Surgery: Pleural fluid drainage: Chest tube placement
* Protocol Image #1: Once the chest tube is placed, imaging is obtained within 24-48 hours to assess the fluid drainage.
* Other: Surgical Consultation
* Surgery: The surgical arm will have either open surgery or a VATS approach at the discretion of the surgeon
* Protocol Image #2: Chest X-ray PA/Lateral: The morning after intervention completion (surgery or last dose of IPFT), a chest X-ray PA/lateral will be obtained
* Quality of Life: 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

Group Type ACTIVE_COMPARATOR

Surgery

Intervention Type PROCEDURE

The surgical arm will have either open surgery or a Video assisted Thoracoscopic Surgery (VATS) approach at the discretion of the surgeon

Pleural Sampling

Intervention Type PROCEDURE

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

Pleural fluid drainage

Intervention Type PROCEDURE

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.

Protocol Image #1

Intervention Type RADIATION

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.

Surgical Consultation

Intervention Type OTHER

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.

Protocol Image #2: Chest X-ray PA/Lateral

Intervention Type RADIATION

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.

Quality of Life

Intervention Type BEHAVIORAL

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

Interventions

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Intrapleural Medications

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 DRUG

Surgery

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

Pleural Sampling

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

Pleural fluid drainage

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

Protocol Image #1

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

Surgical Consultation

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

Protocol Image #2: Chest X-ray PA/Lateral

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

Quality of Life

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

Other Intervention Names

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IPFT

Eligibility Criteria

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Inclusion Criteria

* Age \>18 years
* Clinical presentation compatible with pleural infection (fever or leukocytosis, elevated procalcitonin, elevated C-reactive protein (CRP))
* Pleural fluid requiring drainage that is either:

* Macroscopically purulent or
* Positive on culture for bacterial infection or
* Positive for bacteria on gram stain or
* Lactate dehydrogenase (LDH) \> 1000 IU/L or
* Glucose \<40 mg/dL

Exclusion Criteria

* Age \<18 years
* Unable to give consent (No surrogate consent of legally authorized representatives allowed for this study)
* Not proficient in English
* History of prior ipsilateral empyema
* Has known sensitivity to DNase or alteplase
* History of intracranial hemorrhage or acute intracranial hemorrhage
* History of stroke, hemorrhage, or trauma within the last 3 months
* Has had prior surgery on the side of the pleural infection
* Patients who are pregnant or lactating
* Expected survival less than 6 months from a different pathology to this pleural infection based on clinical judgment
* Has a tunneled pleural catheter in place
* Patients on anticoagulation that cannot be interrupted for surgical intervention
* Patients with known or suspected malignant pleural effusion
* Patients with renal failure (Creatinine clearance \<30)
* Prior history of or concern for chylothorax or pseudochylothorax
* Vulnerable populations: prisoners
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Swedish Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jed Gorden, MD

Role: PRINCIPAL_INVESTIGATOR

Swedish Cancer Institute

Locations

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Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Wilshire CL, Jackson AS, Vallieres E, Bograd AJ, Louie BE, Aye RW, Farivar AS, White PT, Gilbert CR, Gorden JA. Effect of Intrapleural Fibrinolytic Therapy vs Surgery for Complicated Pleural Infections: A Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237799. doi: 10.1001/jamanetworkopen.2023.7799.

Reference Type DERIVED
PMID: 37043201 (View on PubMed)

Other Identifiers

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STUDY2018000278

Identifier Type: -

Identifier Source: org_study_id

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