The Safety and Efficacy of Fibrinolysis in Patients With an Indwelling Pleural Catheter for Multi-loculated Malignant Pleural Effusion.

Phase 2

Withdrawn

• Conditions: Pleural Effusion; Cancer, Lung
• Interventions: Drug: tPA standard dosage; Drug: tPA low dosage

• Registration Number: NCT03678090
• Lead Sponsor: Yale University

Brief Summary

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 Timeline

• Study First Submitted: 2018-09-18
• Study First Submitted QC: 2018-09-18
• Study First Posted: 2018-09-19
• Study Start: 2018-12-01
• Primary Completion: 2020-02-28
• Study Completion: 2020-02-28
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-03
• Last Update Posted: 2020-03-05

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• 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

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Exclusion Criteria

• Age <18
• Expected survival less than 14 days
• Known allergy or intolerance to tissue plasminogen activator

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
tPA standard dosage	tPA standard dosage	Tissue Plasminogen Activator (tPA) dose of 10 to 25 mg.
tPA low dosage	tPA low dosage	tPA dose of 2.5mg

Primary Outcome Measures

Name	Time	Method
Improvement on the modified Borg dyspnea scale after tPA	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.
Improvement in patient chest X-ray	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.

Secondary Outcome Measures

Name	Time	Method
Time to recurrent loculation	up to 90 days	In patients where tPA restores effective drainage, the time to and rate of patients who experience recurrent ineffective drainage due to loculation
Rate of pleurodesis	up to 90 days	The rate of patients who are able to have the indwelling pleural catheter removed.
Improvements in dyspnea using the modified Borg scale	up to 40 days	Change in modified Borg dyspnea scale obtained at initial clinic visit compared to scale at the end of the study protocol.