Clinical trial NCT03213834: Fibrinolytic Therapy Versus Medical Thoracoscopy
Official title: Fibrinolytic Therapy Versus Medical Thoracoscopy for Treatment of Severe Pleural Infection: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pleural Diseases
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2017-07-11
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomly assigned to receive one of two standard-of-care treatments for severe pleural infection.
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective randomized clinical trial is to compare two currently accepted standard-of-care treatment strategies: medical thoracoscopy as compared to instillation of intrapleural tissue plasminogen activator (TPA) and human recombinant deoxyribonuclease (DNase) for the management of complicated pleural infections in adults as defined as complicated parapneumonic effusions or pleural empyema.

Detailed description: Pleural infection (empyema or complex parapneumonic effusion \[CPPE\]) represents one of the common clinical diagnoses encountered in clinical practice in the United States (US) and worldwide. The incidence of pleural infection continues to rise with an annual incidence of approximately 65,000 in the US and United Kingdom (UK). It is associated with substantial morbidity and mortality as well as increased hospital costs despite advances in medical diagnostic and therapeutic strategies. The overall mortality of pleural infection approaches 20% and it is above 30% in elderly patients over 65 years and immunocompromised patients.

Treatment of CPPE or empyema requires antibiotics and drainage of the pleural cavity.3 However, in about 30% of cases, it is difficult to remove the fluid due to loculations, septations and increased viscosity of the pleural fluid, and around 20% will need surgical intervention to adequately treat the pleural infection.

Specific Aim 1:

To compare the efficacy of early medical thoracoscopy versus fibrinolytic therapy (tPA/DNase) in patients with complicated parapneumonic effusions or pleural empyema.

CPPE is defined as non-purulent effusion in a patient with clinical evidence of infection such as fever and/or elevated blood leukocyte count and/or elevated CRP, with pleural fluid pH ≤ 7.2 (measured by blood-gas analyzer), or pleural fluid glucose \< 60 mg/dl or pleural fluid LDH \>1000 IU/L26. Empyema is defined as pus within the pleural space and/or presence of bacteria on pleural fluid Gram stain or culture.

For patients to be considered for the trial they need to fulfill one of the following criteria: 1) CPPE along with evidence of septated pleural effusion on pleural ultrasonography and/or chest CT scan or 2) empyema.

Eligibility criteria: Inclusion Criteria:

1. CPPE along with evidence of septated pleural effusion on pleural ultrasonography and/or chest CT scan
2. empyema.

Exclusion Criteria:

1. age \<18 years;
2. Pregnancy
3. inability to give informed written consent;
4. previous thoracic surgery or thrombolytic therapy for pleural infection;
5. medical thoracoscopy cannot be performed within 48 hours;
6. inability to tolerate procedure due to hemodynamic instability or severe hypoxemia;
7. inability to correct coagulopathy;
8. presence of a homogeneously echogenic effusion on pleural US27 -

Primary outcomes:
measure: Number of Hospital Days for Required to Treat Complicated Parapneumonic Effusions or Pleural Empyema.
timeFrame: 30 days starting on day of admission
Secondary outcomes:
measure: Duration of Chest Tube
timeFrame: 30 days starting on day of admission
measure: Duration of Entire Hospital Stay for Complete Treatment of Pleural Infection
timeFrame: 30 days starting on day of admission
measure: Treatment Failure
timeFrame: 30 days starting on day of admission
measure: Number of Participants With Adverse Events
timeFrame: 30 days starting on day of admission
measure: Mortality
timeFrame: 30 days starting on day of admission
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Hiren Mehta, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kheir F, Thakore S, Mehta H, Jantz M, Parikh M, Chee A, Kaphle U, Sisnega C, Fernandez-Bussy S, Majid A. Intrapleural Fibrinolytic Therapy versus Early Medical Thoracoscopy for Treatment of Pleural Infection. Randomized Controlled Clinical Trial. Ann Am Thorac Soc. 2020 Aug;17(8):958-964. doi: 10.1513/AnnalsATS.202001-076OC.