Pleural DiseasesPhase 4NCT03213834
Fibrinolytic Therapy Versus Medical Thoracoscopy
A Phase 4 study testing Chest thoracoscopy, Chest fibrinolytic therapy and tPA in people with Pleural Diseases, run by University of Florida at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Pleural Diseases
- What is being tested?
- Chest thoracoscopy, Chest fibrinolytic therapy and tPA
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2017to 4 Feb 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CPPE along with evidence of septated pleural effusion on pleural ultrasonography and/or chest CT scan
- empyema.
Who cannot join
- 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 -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Fibrinolytic Therapy Versus Medical Thoracoscopy for Treatment of Severe 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 complicated pleural infections in adults as defined as complicated parapneumonic effusions or pleural empyema.
Read the 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.
- Conditions
- Pleural Diseases
- Being tested
- Chest thoracoscopy, Chest fibrinolytic therapy, tPA, DNase
- Medical subject headings
- Pleural Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chest thoracoscopyProcedure or surgery
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 therapyProcedure or surgery
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.
tPADrug
Also called Actilyse
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.
DNaseDrug
Also called pulmozyme
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 group | Role | What they receive |
|---|---|---|
| Thoracoscopy Arm | Active comparator | Consisting of chest thoracoscopy Receives: Procedure: Chest thoracoscopy |
| Fibrinolytic Therapy Arm | Active comparator | Consisting of chest fibrinolytic therapy Receives: Procedure: Chest fibrinolytic therapy; Drug: tPA; Drug: DNase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Hospital Days for Required to Treat Complicated Parapneumonic Effusions or Pleural Empyema.
Time between initiation of treatment and hospital discharge
Measured: 30 days starting on day of admission
Secondary outcomes (5)
Duration of Chest Tube
The number of days, during the hospital admission, where the patient demonstrated chest tube drainage
Measured: 30 days starting on day of admission
Duration of Entire Hospital Stay for Complete Treatment of Pleural Infection
Number of days patient registered as in-house for treatment of pleural infection
Measured: 30 days starting on day of admission
Treatment Failure
Following intervention, if patient requires (1) surgical intervention (VATS, open thoracotomy), (2) an additional chest tube, or (3) a repeat procedure
Measured: 30 days starting on day of admission
Number of Participants With Adverse Events
Number of participants who experienced documented adverse events during their hospital stays
Measured: 30 days starting on day of admission
Mortality
In hospital and 30 day mortality measures
Measured: 30 days starting on day of admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start14 Sep 2017
- Primary completion4 Feb 2020
- Study completion4 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pleural DiseasesStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomly assigned to receive one of two standard-of-care treatments for severe pleural infection.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hiren Mehta, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03213834
- Sponsor's protocol ID
- IRB201700012
- Status last verified
- Sep 2023
- First submitted
- 7 Jul 2017
- Last updated
- 20 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32421353
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibrinolytic Therapy Versus Medical Thoracoscopy for Treatment of Severe Pleural Infection: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03213834
- Acronym / sponsor ID
- IRB201700012
- Conditions
- Pleural Diseases
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- 14 Sep 2017 (actual)
- Primary completion
- 4 Feb 2020 (actual)
- Study completion
- 4 Feb 2020 (actual)
- First posted
- 11 Jul 2017 (actual)
- Results
- Posted 20 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomly assigned to receive one of two standard-of-care treatments for severe pleural infection.
| Arm | Type | Receives |
|---|---|---|
| Thoracoscopy Arm | Active comparator | Procedure: Chest thoracoscopyConsisting of chest thoracoscopy |
| Fibrinolytic Therapy Arm | Active comparator | Procedure: Chest fibrinolytic therapy, Drug: tPA, Drug: DNaseConsisting of chest fibrinolytic therapy |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- CPPE along with evidence of septated pleural effusion on pleural ultrasonography and/or chest CT scan
- empyema.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chest thoracoscopyThoracoscopy 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 | Procedure or surgery | Thoracoscopy Arm |
| Chest fibrinolytic therapyA 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. | Procedure or surgery | Fibrinolytic Therapy Arm |
| tPAAlso: ActilysetPA administered intrapleurally through the chest tube followed by saline flush. The intrapleural therapy will be given twice daily for a maximum of 6 doses. | Drug | Fibrinolytic Therapy Arm |
| DNaseAlso: pulmozymeDNase administered intrapleurally through the chest tube followed by saline flush. The intrapleural therapy will be given twice daily for a maximum of 6 doses. | Drug | Fibrinolytic Therapy Arm |
Primary outcome
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
5 secondary outcomes
Duration of Chest Tube
Time frame: 30 days starting on day of admission
Duration of Entire Hospital Stay for Complete Treatment of Pleural Infection
Time frame: 30 days starting on day of admission
Treatment Failure
Time frame: 30 days starting on day of admission
Number of Participants With Adverse Events
Time frame: 30 days starting on day of admission
Mortality
Time frame: 30 days starting on day of admission
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32421353Kheir 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hiren Mehta, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Chest thoracoscopy, Chest fibrinolytic therapy and tPA in people with Pleural Diseases, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Hospital Days for Required to Treat Complicated Parapneumonic Effusions or Pleural Empyema. (time frame: 30 days starting on day of admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03213834, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2024.