Pleural Infection, Empyema, Pleural Diseases, Parapneumonic Effusion
Conditions
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.
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
Interventions
DRUGtissue 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
PROCEDUREMedical Thoracoscopy
Medical thoracoscopy will be performed as per standard protocols.
Sponsors
Tulane University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Total Length of Hospital Stay | 12 week follow up period | Total days spent in the hospital |
| Number of Participants Necessitating Intervention After the Assigned Treatment | 12 week follow up period | 1. Need for surgical intervention (VATS, Open Thoracotomy) in any arm 2. Need for additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to treatment failure 3. Need of additional chest tube or additional fibrinolytic doses in the fibrinolytic therapy arm due to treatment failure |
| Adverse Events | 12 week follow up period | any Adverse events (pain, bleeding) |
| In Hospital and 30-day Mortality | 30 days | Death of a patient while being hospitalized or up to 30 days after |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 16 |
| Medical Thoracoscopy Group Patients randomized to the Thoracoscopy group will undergo medical thoracoscopy.
Medical Thoracoscopy: Medical thoracoscopy will be performed as per standard protocols. | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Fibrinolytic Therapy Group | Medical Thoracoscopy Group | Total |
|---|---|---|---|
| Age, Continuous | 58 years | 65 years | 64 years |
| Number of subjects with community acquired pleural infection | 12 Participants | 12 Participants | 24 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 14 Participants | 24 Participants |
| Ultrasonographic estimated pleural effusion volume,Moderate | 13 Participants | 13 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 1 / 16 |
| other Total, other adverse events | 1 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Duration of Hospital Stay After Intervention
duration of hospital stay in days from time of procedure to discharge from hospital.
Time frame: 12 week follow up period
Population: All participants received one of the assigned intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fibrinolytic Therapy Group | Duration of Hospital Stay After Intervention | 4 days |
| Medical Thoracoscopy Group | Duration of Hospital Stay After Intervention | 2 days |
Secondary
Adverse Events
any Adverse events (pain, bleeding)
Time frame: 12 week follow up period
Population: All participants received assigned intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fibrinolytic Therapy Group | Adverse Events | 1 Participants |
| Medical Thoracoscopy Group | Adverse Events | 1 Participants |
Secondary
In Hospital and 30-day Mortality
Death of a patient while being hospitalized or up to 30 days after
Time frame: 30 days
Population: All participants received assigned intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fibrinolytic Therapy Group | In Hospital and 30-day Mortality | 0 Participants |
| Medical Thoracoscopy Group | In Hospital and 30-day Mortality | 1 Participants |
Secondary
Number of Participants Necessitating Intervention After the Assigned Treatment
1. Need for surgical intervention (VATS, Open Thoracotomy) in any arm 2. Need for additional chest tube and/or fibrinolytic therapy in the medical thoracoscopy arm due to treatment failure 3. 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
Population: All participants received assigned intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fibrinolytic Therapy Group | Number of Participants Necessitating Intervention After the Assigned Treatment | 3 Participants |
| Medical Thoracoscopy Group | Number of Participants Necessitating Intervention After the Assigned Treatment | 4 Participants |
Secondary
Total Length of Hospital Stay
Total days spent in the hospital
Time frame: 12 week follow up period
Population: All participants received assigned intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fibrinolytic Therapy Group | Total Length of Hospital Stay | 6 days |
| Medical Thoracoscopy Group | Total Length of Hospital Stay | 3.5 days |