Fibrinolytic Therapy Versus Medical Thoracoscopy

Pleural Diseases Clinical Trial

Official title:

Fibrinolytic Therapy Versus Medical Thoracoscopy for Treatment of Severe Pleural Infection: A Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03213834
• Other study ID #: IRB201700012
• Status: Completed
• Phase: Phase 4
• Start date: September 14, 2017
• Est. completion date: February 4, 2020

Study information

• Verified date: September 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: February 4, 2020
• Est. primary completion date: February 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 -

Related Conditions & MeSH terms

• Pleural Diseases

Intervention

Procedure:
• Chest thoracoscopy
Thoracoscopy will be performed as per standard protocols, with patient lateral decubitus position. Ten mLs of fluid will be collected to check for biomarkers. Adhesiolysis will be attempted and pleural irrigation will be done. At the end of the procedure, a drain will be inserted and connected to an underwater seal with a negative pressure suction
• Chest fibrinolytic therapy
A chest tube will be inserted under ultrasonography into the most dependent area of the pleural effusion or into the largest loculation in patients with multi-loculated effusions. A of DNase and tPA will be given. Concurrent tPA and DNase will be administered intrapleurally through the chest tube followed by saline flush. The tube will then be clamped for 120 minutes and after which it will be connected back to wall suction. The intrapleural therapy will be given twice daily for a maximum of 6 doses.

Drug:
• tPA
tPA administered intrapleurally through the chest tube followed by saline flush. The intrapleural therapy will be given twice daily for a maximum of 6 doses.
• DNase
DNase administered intrapleurally through the chest tube followed by saline flush. The intrapleural therapy will be given twice daily for a maximum of 6 doses.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 T — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Hospital Days for Required to Treat Complicated Parapneumonic Effusions or Pleural Empyema.	Time between initiation of treatment and hospital discharge	30 days starting on day of admission
Secondary	Duration of Chest Tube	The number of days, during the hospital admission, where the patient demonstrated chest tube drainage	30 days starting on day of admission
Secondary	Duration of Entire Hospital Stay for Complete Treatment of Pleural Infection	Number of days patient registered as in-house for treatment of pleural infection	30 days starting on day of admission
Secondary	Treatment Failure	Following intervention, if patient requires (1) surgical intervention (VATS, open thoracotomy), (2) an additional chest tube, or (3) a repeat procedure	30 days starting on day of admission
Secondary	Number of Participants With Adverse Events	Number of participants who experienced documented adverse events during their hospital stays	30 days starting on day of admission
Secondary	Mortality	In hospital and 30 day mortality measures	30 days starting on day of admission