Management of Pleural Space Infections

Swedish Medical Center

Status and phase: Completed; Phase 4

Conditions: Empyema, Pleural; Parapneumonic Effusion

Treatments: Drug: Intrapleural Medications; Radiation: Protocol Image #2: Chest X-ray PA/Lateral; Radiation: Protocol Image #1; Behavioral: Quality of Life; Procedure: Pleural Sampling; Procedure: Surgery; Other: Surgical Consultation; Procedure: Pleural fluid drainage

Study type: Interventional

Funder types: Other

Identifiers

NCT03873766

STUDY2018000278

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Intrapleural fibrinolytic therapy (IPFT)

Active Comparator group

Description:

* 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

Treatment:

Behavioral: Quality of Life

Procedure: Pleural Sampling

Other: Surgical Consultation

Procedure: Pleural fluid drainage

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

Radiation: Protocol Image #1

Drug: Intrapleural Medications

Surgery

Active Comparator group

Description:

* 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

Treatment:

Behavioral: Quality of Life

Procedure: Pleural Sampling

Other: Surgical Consultation

Procedure: Pleural fluid drainage

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

Radiation: Protocol Image #1

Procedure: Surgery