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Completed

NCT Number: NCT03213834

Fibrinolytic Therapy Versus Medical Thoracoscopy

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.

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Key information

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Florida

Gainesville, Florida, 32611, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 -

Treatment and study plan

Chest thoracoscopy

Procedure

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

Procedure

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.

tPA

Drug

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

DNase

Drug

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

Primary outcomes

  1. Number of Hospital Days for Required to Treat Complicated Parapneumonic Effusions or Pleural Empyema.

    Time frame: 30 days starting on day of admission

    Time between initiation of treatment and hospital discharge

Secondary outcomes

  1. Duration of Chest Tube

    Time frame: 30 days starting on day of admission

    The number of days, during the hospital admission, where the patient demonstrated chest tube drainage

  2. Duration of Entire Hospital Stay for Complete Treatment of Pleural Infection

    Time frame: 30 days starting on day of admission

    Number of days patient registered as in-house for treatment of pleural infection

  3. Treatment Failure

    Time frame: 30 days starting on day of admission

    Following intervention, if patient requires (1) surgical intervention (VATS, open thoracotomy), (2) an additional chest tube, or (3) a repeat procedure

  4. Number of Participants With Adverse Events

    Time frame: 30 days starting on day of admission

    Number of participants who experienced documented adverse events during their hospital stays

  5. Mortality

    Time frame: 30 days starting on day of admission

    In hospital and 30 day mortality measures

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Jul 11, 2017
Registry last updated
Feb 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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