Fibrinolytic Therapy Versus Medical Thoracoscopy

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

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.

Study Overview

• Status: Completed
• Conditions: Pleural Diseases
• Intervention / Treatment: Procedure: Chest thoracoscopy; Procedure: Chest fibrinolytic therapy; Drug: tPA; Drug: DNase

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thoracoscopy Arm; Consisting of chest thoracoscopy	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
Active Comparator: Fibrinolytic Therapy Arm; Consisting of chest fibrinolytic therapy	Procedure: 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.; Other Names: Actilyse; Drug: 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.; Other Names: pulmozyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Mortality	In hospital and 30 day mortality measures	30 days starting on day of admission

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Hiren Mehta, MD, University of Florida

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2017
• Primary Completion (Actual): February 4, 2020
• Study Completion (Actual): February 4, 2020

Study Registration Dates

• First Submitted: July 7, 2017
• First Submitted That Met QC Criteria: July 7, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Pleural Diseases; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: IRB201700012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No