Fibrinolytic Therapy Versus Medical Thoracoscopy

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03213834

Enrollment

Registered

2017-07-11

Start date

2017-09-14

Completion date

2020-02-04

Last updated

2024-02-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pleural Diseases

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.

Interventions

PROCEDUREChest 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

PROCEDUREChest 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.

DRUGtPA

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.

DRUGDNase

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (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

Intervention model description

Subjects will be randomly assigned to receive one of two standard-of-care treatments for severe pleural infection.

Eligibility

Sex/Gender

ALL

Age

18 Years to 90 Years

Healthy volunteers

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 -

Design outcomes

Primary

Measure	Time frame	Description
Number of Hospital Days for Required to Treat Complicated Parapneumonic Effusions or Pleural Empyema.	30 days starting on day of admission	Time between initiation of treatment and hospital discharge

Secondary

Measure	Time frame	Description
Duration of Chest Tube	30 days starting on day of admission	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	30 days starting on day of admission	Number of days patient registered as in-house for treatment of pleural infection
Treatment Failure	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
Number of Participants With Adverse Events	30 days starting on day of admission	Number of participants who experienced documented adverse events during their hospital stays
Mortality	30 days starting on day of admission	In hospital and 30 day mortality measures

Countries

United States

Participant flow

Recruitment details

The study participants comprised a convenience sample of adults with CPPE or empyema who presented to the UFHealth pulmonary medicine service, met all inclusion / exclusion criteria, and agreed to participate.

Pre-assignment details

After consent, but prior to randomization, all participants underwent diagnostic thoracentesis and confirmation of pleural infection.

Participants by arm

Arm	Count
Thoracoscopy Arm Consisting of chest thoracoscopy 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	3
Fibrinolytic Therapy Arm Consisting of chest fibrinolytic therapy 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. 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.	2
Total	5

Baseline characteristics

Characteristic	Fibrinolytic Therapy Arm	Total	Thoracoscopy Arm
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	1 Participants	1 Participants
Age, Categorical Between 18 and 65 years	2 Participants	4 Participants	2 Participants
Race and Ethnicity Not Collected	—	0 Participants	—
Region of Enrollment United States	2 participants	5 participants	3 participants
Sex: Female, Male Female	2 Participants	4 Participants	2 Participants
Sex: Female, Male Male	0 Participants	1 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 2
other Total, other adverse events	0 / 3	0 / 2
serious Total, serious adverse events	0 / 3	0 / 2