Management of Pleural Space Infections

Summary

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.

Conditions

• Empyema, Pleural
• Parapneumonic Effusion

Interventions

DRUG

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).

PROCEDURE

Surgery

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

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

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.

RADIATION

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.

OTHER

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.

RADIATION

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.

BEHAVIORAL

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

Sponsors & Collaborators

• Swedish Medical Center

  lead OTHER

Principal Investigators

• Jed Gorden, MD · Swedish Cancer Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-04-01

Primary Completion

2022-03-11

Completion

2022-03-11

FDA Drug

Yes

Countries

• United States

Study Locations