Management of Pleural Space Infections

NCT03873766 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: STUDY2018000278
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (2)

• Feasibility of the proposed study algorithm as measured by percent of subjects enrolled to study completion, percent of subjects randomized but did not complete the study, and percent of health care professional protocol deviation

  • Test the feasibility of the proposed study algorithm to compare Intrapleural fibrinolytic therapy (IPFT) to surgical intervention as measured by percent enrollment to completion of study algorithm and multidisciplinary participation in adherence to the algorithm.

  From patient identification to 1 year post discharge

• Subject identification and accrual as measured by the percent of patients not screened and randomized and the time to accrual of 20 patients of the number of patients accrued in one year

  Subject identification and accrual as measured by the percent of patients not screened and randomized and the time to accrual of 20 patients of the number of patients accrued in one year

  From patient identification to 1 year post discharge

Secondary Outcomes (6)

• Radiographic improvement

  From date of protocol Image #1 (once the chest tube is placed, protocol image #1 is obtained within 24-48 hours) to date of protocol Image #2 (the morning after intervention, approximately 12-24 hours after intervention)

• Number of participants who have treatment failures needing further treatment crossover (IPFT to surgery; surgery to IPFT)

  From patient identification to 1 year post discharge

• Number of participants with procedure related complications

  From intervention with IPFT or surgery to date of discharge from hospital, usually 7-10 days

• Quality of life Surveys: 36-Item Short Form Survey (SF-36)

  Quality of life will be measured at 30 day and 90 day clinical follow-up

• Cost comparison

  From date of intervention with IPFT or surgery to date of discharge from hospital, usually 7-10 days

Study Arms (2)

Intrapleural fibrinolytic therapy (IPFT)

ACTIVE COMPARATOR

* 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

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

Surgery

ACTIVE COMPARATOR

* 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

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

Interventions

Intrapleural Medications 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).

Also known as: IPFT

Intrapleural fibrinolytic therapy (IPFT)

Surgery PROCEDURE

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

Surgery

Pleural Sampling 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

Intrapleural fibrinolytic therapy (IPFT); Surgery

Pleural fluid drainage 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.

Intrapleural fibrinolytic therapy (IPFT); Surgery

Protocol Image #1 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.

Intrapleural fibrinolytic therapy (IPFT); Surgery

Surgical Consultation 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.

Intrapleural fibrinolytic therapy (IPFT); Surgery

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

Intrapleural fibrinolytic therapy (IPFT); Surgery

Quality of Life 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

Intrapleural fibrinolytic therapy (IPFT); Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Medical Center: lead

Study Sites (1)

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• 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.

  PMID: 37043201 DERIVED

MeSH Terms

Conditions

Empyema, Pleural

Interventions

Surgical Procedures, Operative; Quality of Life

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Empyema; Suppuration; Pleural Diseases; Respiratory Tract Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• Jed Gorden, MD

  Swedish Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized to either IPFT or surgery for treatment of their complex pleural space infection

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: March 13, 2019
• Study Start: April 1, 2019
• Primary Completion: March 11, 2022
• Study Completion: March 11, 2022
• Last Updated: November 22, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)