Pleural EffusionPhase 2NCT03678090
The Safety and Efficacy of Fibrinolysis in Patients With an Indwelling Pleural Catheter for Multi-loculated Malignant Pleural Effusion.
A Phase 2 study testing tPA standard dosage and tPA low dosage in people with Pleural Effusion and Cancer, Lung, run by Yale University.
Trial summary
The safety and efficacy of fibrinolysis in patients with an indwelling pleural catheter for multi-loculated malignant pleural effusion. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pleural Effusion, Cancer, Lung
- What is being tested?
- tPA standard dosage and tPA low dosage
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2018to 28 Feb 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Malignant Pleural Effusion MPE (either cytology proven or recurrent exudative pleural effusion in the context of histologically proven cancer)
- Presence of an indwelling pleural catheter (IPC)
- Nondraining IPC (defined as <50 mL of drainage on the past three drainage attempts) not responding to routine saline flush to assure patency
- Residual pleural fluid remaining on chest x-ray (CXR) or ultrasound
- Dyspnea deemed attributable to the effusion (i.e. symptomatic loculations), as assessed by the treating chest physician and using the modified Borg scale
- Presence of written informed consent from the patient or surrogate
Who cannot join
- Age <18
- Expected survival less than 14 days
- Known allergy or intolerance to tissue plasminogen activator
About this study
Official title: The Safety and Efficacy of Fibrinolysis in Patients With an Indwelling Pleural Catheter for Multi-loculated Malignant Pleural Effusion: a Prospective Randomized Trial
The safety and efficacy of fibrinolysis in patients with an indwelling pleural catheter for multi-loculated malignant pleural effusion.
Read the detailed description
Malignant pleural effusion (MPE) is a condition where fluid accumulates in the chest (pleural space) due to the presence of cancer. The malignancy may is usually metastatic from the lung, breast, or elsewhere and the presence of a MPE usually causes significant morbidity, particularly shortness of breath. Once a MPE develops, the patient's disease cannot be cured, but symptoms of dyspnea can be palliated.
Malignant effusions usually recur after thoracentesis, a procedure to remove the fluid. Upon recurrence, patients usually undergo placement of an indwelling pleural catheter (IPC). This is a small tube that drains fluid from inside the chest into a bottle to be discarded. It is very effective at treating shortness of breath and is safe.
On occasion, these catheters stop functioning, leading to an increase in the effusion again. This may be due to small amounts of blood or debris such as fibrin that clog the catheter, or it may be related to the pleural fluid becoming too thick to drain. Medication, namely tissue plasminogen activator (tPA), can be placed inside the catheter to promote drainage. With simple clogging, the tPA acts like "Draino." For fluid that has become too thick and pleural effusions that won't drain due to loculations, the tPA helps dissolve debris in the pleural fluid to promote drainage. Without this drainage, patients remain impaired due to shortness of breath related to the fluid.
tPA is effective at draining the fluid when debris has clogged the catheter or the pleural space. However, the exact dosing is unknown. For "simple" clogging, small doses may be used. When extensive loculations are present, large doses may be required to help the patient. Two retrospective studies have looked at very small doses of tPA placed through the IPC with the goal of breaking up the clogs in the catheter itself. These studies used between 2 and 5 mg of tPA.1,2 At Yale-New Haven Hospital, 25 mg has typically been used due to historical preference. It is unknown whether high doses of tPA improve its therapeutic efficacy.
The investigators hypothesize that higher dose fibrinolysis with 25mg of tPA (compared with 2.5 mg) will provide more effective clearance of fluid loculations, resulting in improved radiographic appearance and less shortness of breath without an increased risk of complications, such as bleeding.
- Conditions
- Pleural Effusion, Cancer, Lung
- Being tested
- tPA standard dosage, tPA low dosage
- Medical subject headings
- Pleural Effusion, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tPA standard dosageDrug
Also called tissue plasminogen activator
Tissue plasminogen activator 25mg dosage
tPA low dosageDrug
Also called tissue plasminogen activator
Tissue plasminogen activator 2.5mg
| Study group | Role | What they receive |
|---|---|---|
| tPA standard dosage | Active comparator | Tissue Plasminogen Activator (tPA) dose of 10 to 25 mg. Receives: Drug: tPA standard dosage |
| tPA low dosage | Experimental | tPA dose of 2.5mg Receives: Drug: tPA low dosage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in patient chest X-ray
Defined as change in percentage of hemithorax occupied by the pleural opacity on chest X-ray from the baseline chest X-ray to the X-ray at the end of the study protocol.
Measured: up to 40 days
Improvement on the modified Borg dyspnea scale after tPA
Change in modified Borg dyspnea scale obtained at clinic visit where tPA is administered compared to modified Borg dyspnea scale obtained after post-tPA drainage.
Measured: up to 40 days
Secondary outcomes (3)
Time to recurrent loculation
In patients where tPA restores effective drainage, the time to and rate of patients who experience recurrent ineffective drainage due to loculation
Measured: up to 90 days
Rate of pleurodesis
The rate of patients who are able to have the indwelling pleural catheter removed.
Measured: up to 90 days
Improvements in dyspnea using the modified Borg scale
Change in modified Borg dyspnea scale obtained at initial clinic visit compared to scale at the end of the study protocol.
Measured: up to 40 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start1 Dec 2018 (estimated)
- Primary completion28 Feb 2020
- Study completion28 Feb 2020
Why it stopped: Local IRB recommended IND exemption from FDA, study timeline not able to be met.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pleural EffusionStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Godfrey, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03678090
- Sponsor's protocol ID
- 2000024040
- Status last verified
- Mar 2020
- First submitted
- 18 Sep 2018
- Last updated
- 5 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy of Fibrinolysis in Patients With an Indwelling Pleural Catheter for Multi-loculated Malignant Pleural Effusion: a Prospective Randomized Trial
- ClinicalTrials.gov ID
- NCT03678090
- Acronym / sponsor ID
- 2000024040
- Conditions
- Pleural Effusion, Cancer, Lung
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Local IRB recommended IND exemption from FDA, study timeline not able to be met.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 1 Dec 2018 (estimated)
- Primary completion
- 28 Feb 2020 (actual)
- Study completion
- 28 Feb 2020 (actual)
- First posted
- 19 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The safety and efficacy of fibrinolysis in patients with an indwelling pleural catheter for multi-loculated malignant pleural effusion.
Detailed description
Malignant pleural effusion (MPE) is a condition where fluid accumulates in the chest (pleural space) due to the presence of cancer. The malignancy may is usually metastatic from the lung, breast, or elsewhere and the presence of a MPE usually causes significant morbidity, particularly shortness of breath. Once a MPE develops, the patient's disease cannot be cured, but symptoms of dyspnea can be palliated.
Malignant effusions usually recur after thoracentesis, a procedure to remove the fluid. Upon recurrence, patients usually undergo placement of an indwelling pleural catheter (IPC). This is a small tube that drains fluid from inside the chest into a bottle to be discarded. It is very effective at treating shortness of breath and is safe.
On occasion, these catheters stop functioning, leading to an increase in the effusion again. This may be due to small amounts of blood or debris such as fibrin that clog the catheter, or it may be related to the pleural fluid becoming too thick to drain. Medication, namely tissue plasminogen activator (tPA), can be placed inside the catheter to promote drainage. With simple clogging, the tPA acts like "Draino." For fluid that has become too thick and pleural effusions that won't drain due to loculations, the tPA helps dissolve debris in the pleural fluid to promote drainage. Without this drainage, patients remain impaired due to shortness of breath related to the fluid.
tPA is effective at draining the fluid when debris has clogged the catheter or the pleural space. However, the exact dosing is unknown. For "simple" clogging, small doses may be used. When extensive loculations are present, large doses may be required to help the patient. Two retrospective studies have looked at very small doses of tPA placed through the IPC with the goal of breaking up the clogs in the catheter itself. These studies used between 2 and 5 mg of tPA.1,2 At Yale-New Haven Hospital, 25 mg has typically been used due to historical preference. It is unknown whether high doses of tPA improve its therapeutic efficacy.
The investigators hypothesize that higher dose fibrinolysis with 25mg of tPA (compared with 2.5 mg) will provide more effective clearance of fluid loculations, resulting in improved radiographic appearance and less shortness of breath without an increased risk of complications, such as bleeding.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tPA standard dosage | Active comparator | Drug: tPA standard dosageTissue Plasminogen Activator (tPA) dose of 10 to 25 mg. |
| tPA low dosage | Experimental | Drug: tPA low dosagetPA dose of 2.5mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Malignant Pleural Effusion MPE (either cytology proven or recurrent exudative pleural effusion in the context of histologically proven cancer)
- Presence of an indwelling pleural catheter (IPC)
- Nondraining IPC (defined as <50 mL of drainage on the past three drainage attempts) not responding to routine saline flush to assure patency
- Residual pleural fluid remaining on chest x-ray (CXR) or ultrasound
- Dyspnea deemed attributable to the effusion (i.e. symptomatic loculations), as assessed by the treating chest physician and using the modified Borg scale
Key exclusion criteria (3 listed)
- Age <18
- Expected survival less than 14 days
- Known allergy or intolerance to tissue plasminogen activator
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 |
|---|---|---|
| tPA standard dosageAlso: tissue plasminogen activatorTissue plasminogen activator 25mg dosage | Drug | tPA standard dosage |
| tPA low dosageAlso: tissue plasminogen activatorTissue plasminogen activator 2.5mg | Drug | tPA low dosage |
Primary outcome
Improvement in patient chest X-ray
Time frame: up to 40 days
Defined as change in percentage of hemithorax occupied by the pleural opacity on chest X-ray from the baseline chest X-ray to the X-ray at the end of the study protocol.
Improvement on the modified Borg dyspnea scale after tPA
Time frame: up to 40 days
Change in modified Borg dyspnea scale obtained at clinic visit where tPA is administered compared to modified Borg dyspnea scale obtained after post-tPA drainage.
3 secondary outcomes
Time to recurrent loculation
Time frame: up to 90 days
Rate of pleurodesis
Time frame: up to 90 days
Improvements in dyspnea using the modified Borg scale
Time frame: up to 40 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2020.
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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.
Mark Godfrey, MD principal investigator
Yale University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing tPA standard dosage and tPA low dosage in people with Pleural Effusion and Cancer, Lung, run by Yale University.
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 6 inclusion and 3 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: withdrawn, as of the sponsor's last update on 5 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Improvement in patient chest X-ray (time frame: up to 40 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Mar 2020.