Fibrinolytic Therapy Versus Medical Thoracoscopy
Primary Purpose
Pleural Diseases
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Chest thoracoscopy
Chest fibrinolytic therapy
tPA
DNase
Sponsored by
About this trial
This is an interventional treatment trial for Pleural Diseases
Eligibility Criteria
Inclusion Criteria:
- CPPE along with evidence of septated pleural effusion on pleural ultrasonography and/or chest CT scan
- empyema.
Exclusion Criteria:
- age <18 years;
- Pregnancy
- inability to give informed written consent;
- previous thoracic surgery or thrombolytic therapy for pleural infection;
- medical thoracoscopy cannot be performed within 48 hours;
- inability to tolerate procedure due to hemodynamic instability or severe hypoxemia;
- inability to correct coagulopathy;
- presence of a homogeneously echogenic effusion on pleural US27 -
Sites / Locations
- University of Florida
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Thoracoscopy Arm
Fibrinolytic Therapy Arm
Arm Description
Consisting of chest thoracoscopy
Consisting of chest fibrinolytic therapy
Outcomes
Primary Outcome Measures
Duration of hospital days for treatment of complicated parapneumonic effusions or pleural empyema.
Time between initiation of treatment and hospital discharge
Secondary Outcome Measures
Duration of chest tube
The number of days, during the hospital admission, where the patient demonstrated chest tube drainage
Duration of entire hospital stay for complete treatment of pleural infection
Number of days patient registered as in-house for treatment of pleural infection
Treatment Failure
Following intervention, if patient requires (1) surgical intervention (VATS, open thoracotomy), (2) an additional chest tube, or (3) a repeat procedure
Frequency of adverse events
Number of recorded adverse events during hospital stay
Mortality
In hospital and 30 day mortality measures
Change in pleural fluid volume
Change in pleural fluid volume on chest CT scan from randomization (day 0) to prior to chest tube removal measured by radiologist blinded to treatment allocation using image J software
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03213834
Brief Title
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
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
September 14, 2017 (Actual)
Primary Completion Date
February 4, 2020 (Actual)
Study Completion Date
February 4, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pleural Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Subjects will be randomly assigned to receive one of two standard-of-care treatments for severe pleural infection.
Masking
Outcomes Assessor
Masking Description
Change in pleural fluid volume on chest CT scan from randomization (day 0) to prior to chest tube removal will be measured by a radiologist blinded to treatment allocation using image J software
Allocation
Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Thoracoscopy Arm
Arm Type
Active Comparator
Arm Description
Consisting of chest thoracoscopy
Arm Title
Fibrinolytic Therapy Arm
Arm Type
Active Comparator
Arm Description
Consisting of chest fibrinolytic therapy
Intervention Type
Procedure
Intervention Name(s)
Chest thoracoscopy
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Chest fibrinolytic therapy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
tPA
Other Intervention Name(s)
Actilyse
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
DNase
Other Intervention Name(s)
pulmozyme
Intervention Description
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.
Primary Outcome Measure Information:
Title
Duration of hospital days for treatment of complicated parapneumonic effusions or pleural empyema.
Description
Time between initiation of treatment and hospital discharge
Time Frame
2 days - 1 week
Secondary Outcome Measure Information:
Title
Duration of chest tube
Description
The number of days, during the hospital admission, where the patient demonstrated chest tube drainage
Time Frame
2 days - 1 week
Title
Duration of entire hospital stay for complete treatment of pleural infection
Description
Number of days patient registered as in-house for treatment of pleural infection
Time Frame
2 days - 1 week
Title
Treatment Failure
Description
Following intervention, if patient requires (1) surgical intervention (VATS, open thoracotomy), (2) an additional chest tube, or (3) a repeat procedure
Time Frame
2 days - 1 week
Title
Frequency of adverse events
Description
Number of recorded adverse events during hospital stay
Time Frame
2 days - 1 week
Title
Mortality
Description
In hospital and 30 day mortality measures
Time Frame
30 days
Title
Change in pleural fluid volume
Description
Change in pleural fluid volume on chest CT scan from randomization (day 0) to prior to chest tube removal measured by radiologist blinded to treatment allocation using image J software
Time Frame
2 days - 1 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
CPPE along with evidence of septated pleural effusion on pleural ultrasonography and/or chest CT scan
empyema.
Exclusion Criteria:
age <18 years;
Pregnancy
inability to give informed written consent;
previous thoracic surgery or thrombolytic therapy for pleural infection;
medical thoracoscopy cannot be performed within 48 hours;
inability to tolerate procedure due to hemodynamic instability or severe hypoxemia;
inability to correct coagulopathy;
presence of a homogeneously echogenic effusion on pleural US27 -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiren Mehta, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Fibrinolytic Therapy Versus Medical Thoracoscopy
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