Fibrinolysis Compared to Thoracoscopy for Pleural Infection

• Sponsor: Tulane University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03468933
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 25.9
• Patients Per Site Per Month: 1.2

Study Details

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 empyema or complicated parapneumonic effusion (CPPE) in adults.

Condition or Disease	Intervention/Treatment	Phase
Pleural Infection; Empyema; Pleural Diseases; Parapneumonic Effusion	Drug: tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase); Procedure: Medical Thoracoscopy	Phase 4

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: Investigators will conduct a prospective randomized clinical trial. Plan is to enroll total of 32 patients and randomize those patients 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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intrapleural Tissue Plasminogen Activator and Deoxyribonuclease Therapy Versus Early Medical Thoracoscopy for Treatment of Pleural Infection: A Randomized Clinical Trial
• Actual Study Start Date: Nov 1, 2017
• Actual Primary Completion Date: Dec 30, 2019
• Actual Study Completion Date: Dec 30, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Duration of Hospital Stay After Intervention [12 week follow up period]

   duration of hospital stay in days from time of procedure to discharge from hospital.

Secondary Outcome Measures

1. Total Length of Hospital Stay [12 week follow up period]

   Total days spent in the hospital

2. Number of Participants Necessitating Intervention After the Assigned Treatment [12 week follow up period]

   Need for surgical intervention (VATS, Open Thoracotomy) in any arm Need for additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to treatment failure Need of additional chest tube or additional fibrinolytic doses in the fibrinolytic therapy arm due to treatment failure

3. Adverse Events [12 week follow up period]

   any Adverse events (pain, bleeding)

4. In Hospital and 30-day Mortality [30 days]

   Death of a patient while being hospitalized or up to 30 days after

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tulane Medical Center Tulane University Section of Pulmonary DiseasesTulane University Section of Pulmonary Diseases	New Orleans	Louisiana	United States	70112

Sponsors and Collaborators

• Tulane University

Investigators

• Principal Investigator: Fayez Kheir, MD, MSc, Tulane University

Study Documents (Full-Text)

• Study Protocol - Jul 1, 2017
• Statistical Analysis Plan - Jul 1, 2017

More Information

Publications

None provided.

• Responsible Party: Fayez Kheir,MD,MSc, MD, MSc, Tulane University
• ClinicalTrials.gov Identifier: NCT03468933
• Other Study ID Numbers: 1070390
• First Posted: Mar 19, 2018
• Last Update Posted: Feb 4, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; Empyema; Pleural Diseases; Plasminogen; Tissue Plasminogen Activator

Study Results

Participant Flow

Arm/Group Title	Fibrinolytic Therapy Group	Medical Thoracoscopy Group
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose	Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fibrinolytic Therapy Group	Medical Thoracoscopy Group	Total
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose	Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.	Total of all reporting groups
Overall Participants	16	16	32
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	58	65	64
Sex: Female, Male (Count of Participants)
Female	6 37.5%	2 12.5%	8 25%
Male	10 62.5%	14 87.5%	24 75%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	16 100%	32 100%
Ultrasonographic estimated pleural effusion volume,Moderate (Count of Participants)
Count of Participants [Participants]	13 81.3%	13 81.3%	26 81.3%
Number of subjects with community acquired pleural infection (Count of Participants)
Count of Participants [Participants]	12 75%	12 75%	24 75%

Outcome Measures

1. Primary Outcome

Title	Duration of Hospital Stay After Intervention
Description	duration of hospital stay in days from time of procedure to discharge from hospital.
Time Frame	12 week follow up period

Outcome Measure Data

Analysis Population Description

All participants received one of the assigned intervention

Arm/Group Title	Fibrinolytic Therapy Group	Medical Thoracoscopy Group
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose	Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.
Measure Participants	16	16
Median (Inter-Quartile Range) [days]	4	2

2. Secondary Outcome

Title	Total Length of Hospital Stay
Description	Total days spent in the hospital
Time Frame	12 week follow up period

Outcome Measure Data

Analysis Population Description

All participants received assigned intervention

Arm/Group Title	Fibrinolytic Therapy Group	Medical Thoracoscopy Group
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose	Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.
Measure Participants	16	16
Median (Inter-Quartile Range) [days]	6	3.5

3. Secondary Outcome

Title	Number of Participants Necessitating Intervention After the Assigned Treatment
Description	Need for surgical intervention (VATS, Open Thoracotomy) in any arm Need for additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to treatment failure Need of additional chest tube or additional fibrinolytic doses in the fibrinolytic therapy arm due to treatment failure
Time Frame	12 week follow up period

Outcome Measure Data

Analysis Population Description

All participants received assigned intervention

Arm/Group Title	Fibrinolytic Therapy Group	Medical Thoracoscopy Group
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose	Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.
Measure Participants	16	16
Count of Participants [Participants]	3 18.8%	4 25%

4. Secondary Outcome

Title	Adverse Events
Description	any Adverse events (pain, bleeding)
Time Frame	12 week follow up period

Outcome Measure Data

Analysis Population Description

All participants received assigned intervention

Arm/Group Title	Fibrinolytic Therapy Group	Medical Thoracoscopy Group
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose	Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.
Measure Participants	16	16
Count of Participants [Participants]	1 6.3%	1 6.3%

5. Secondary Outcome

Title	In Hospital and 30-day Mortality
Description	Death of a patient while being hospitalized or up to 30 days after
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

All participants received assigned intervention

Arm/Group Title	Fibrinolytic Therapy Group	Medical Thoracoscopy Group
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose	Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.
Measure Participants	16	16
Count of Participants [Participants]	0 0%	1 6.3%

Adverse Events

Time Frame	The perioperative period until hospital discharge, an average of 4 weeks per participant
Adverse Event Reporting Description	Definition of adverse event and/or serious adverse event, used to collect adverse event information does not differ from the clinicaltrials.gov.
Arm/Group Title	Fibrinolytic Therapy Group		Medical Thoracoscopy Group
Arm/Group Description	Patients randomized to the Fibrinolytic group will receive intrapleural therapy of combined tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) via chest tube. tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase): Patients will receive intrapleural combination of TPA (10 mg) and DNAse (5 mg). Therapy will be given twice daily for a maximum of 6 dose		Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy. Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols.
All Cause Mortality
	Fibrinolytic Therapy Group		Medical Thoracoscopy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		1/16 (6.3%)
Serious Adverse Events
	Fibrinolytic Therapy Group		Medical Thoracoscopy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Fibrinolytic Therapy Group		Medical Thoracoscopy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory	1/16 (6.3%)	1	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.