Fibrinolysis Compared to Thoracoscopy for Pleural Infection

Fibrinolytic Therapy Versus Medical Thoracoscopy for Treatment of 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 empyema or complex parapneumonic effusion (CPPE) in adults.

Study Overview

• Status: Completed
• Conditions: Pleural Diseases; Pleural Infection
• Intervention / Treatment: Other: Medical Thoracoscopy; Other: Fibrinolytic Group

Detailed Description

Background: Pleural infection (empyema or complex parapneumonic effusion (CPPE)) represents one of the most common clinical diagnoses encountered in clinical practice in the United States (US) It is associated with substantial morbidity and mortality despite advances in medical diagnostic and therapeutic strategies.

Objective: Compare two standard of care treatments: TPA/DNase vs early medical Thoracoscopy

Methods: We will conduct a prospective randomized clinical trial. We plan to enroll a total of 80 patients and randomize them to either Medical Thoracoscopy group or Fibrinolytic Therapy group.

Follow-up will be daily until hospital discharge and at 6 and 12 weeks in the outpatient setting

Primary Outcome: Duration of hospital stay after intervention

Secondary Outcome: Failure rate of assigned treatment and adverse events

Potential Outcome and Benefit: Determine best strategy for treating patients with pleural infection

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects >18 years old with:
• Evidence of empyema or complex parapneumonic effusion

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
• Hemodynamic instability or severe hypoxemia
• Non corrected coagulopathy
• Homogeneously echogenic effusion on pleural ultrasonography

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thoracoscopy group; Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy.	Other: Medical Thoracoscopy; Medical thoracoscopy will be performed as per standard protocols.
Active Comparator: Fibrinolytic group; Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase)	Other: Fibrinolytic Group; Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of hospital stay after intervention	Number of days hospitalized	12 week follow up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days with chest drainage	Number of days with chest drainage	12 week follow up period
Total length of hospital stay	Total days spent in the hospital	12 week follow up period
Failure rate of assigned treatment necessitating intervention	defined as any of the following: Surgical intervention (VATS, open thoracotomy) in the medical thoracoscopy or fibrinolytic therapy arm; Need of additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to clinical non-responsiveness; Need of additional chest tube in the fibrinolytic therapy arm due to clinical non-responsiveness	12 week follow up period
Adverse events	Any adverse event (pain or bleeding)	12 week follow up period
In hospital and 30-day mortality	Death of a patient while being hospitalized or up to 30 days after	30 days
Change in pleural fluid volume on Chest CT scan prior to randomization (day 0) to prior to chest tube removal measured by radiologist blinded to treatment allocation using image J software	Pleural fluid volume measured with CT scan	12 week follow up period
Inflammatory biomarker (CRP) from randomization (day 0), at 6 weeks and 12 weeks respectively	Inflammatory biomarker measure	at randomization and at 6 and12 week follow up visit
Total costs of each treatment modality	Total cost of each of treatment modality	6 and 12 week follow up period

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center

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): July 14, 2017
• Primary Completion (Actual): November 1, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: November 22, 2016
• First Submitted That Met QC Criteria: November 22, 2016
• First Posted (Estimate): November 25, 2016

Study Record Updates

• Last Update Posted (Actual): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Pleural Diseases
• Other Study ID Numbers: 2016P000307

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