Clinical trial NCT03873766: Management of Pleural Space Infections
Official title: Management of Pleural Space Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Empyema, Pleural
Parapneumonic Effusion
Lead sponsor: Swedish Medical Center
Sponsor class: OTHER
First posted: 2019-03-13
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized to either IPFT or surgery for treatment of their complex pleural space infection
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: From patient identification to 1 year post discharge
measure: 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
timeFrame: From patient identification to 1 year post discharge
Secondary outcomes:
measure: Radiographic improvement
timeFrame: 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)
measure: Number of participants who have treatment failures needing further treatment crossover (IPFT to surgery; surgery to IPFT)
timeFrame: From patient identification to 1 year post discharge
measure: Number of participants with procedure related complications
timeFrame: From intervention with IPFT or surgery to date of discharge from hospital, usually 7-10 days
measure: Quality of life Surveys: 36-Item Short Form Survey (SF-36)
timeFrame: Quality of life will be measured at 30 day and 90 day clinical follow-up
measure: Cost comparison
timeFrame: From date of intervention with IPFT or surgery to date of discharge from hospital, usually 7-10 days
measure: Chest tube duration
timeFrame: From date of initiation of intervention of IPFT or surgery (approximately 24-48 hours after patient identification) to date of removal of chest tube, approximately 7 days after placement depending on the intervention and the chest tube output.
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: Swedish Cancer Institute
name: Jed Gorden, MD
role: PRINCIPAL_INVESTIGATOR
References: