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

NCT ID: NCT03678090

Last Updated: 2020-03-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2020-02-28

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.

Conditions

Pleural Effusion; Cancer, Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

tPA standard dosage

Tissue Plasminogen Activator (tPA) dose of 10 to 25 mg.

Group Type: ACTIVE_COMPARATOR

tPA standard dosage

Intervention Type: DRUG

Tissue plasminogen activator 25mg dosage

tPA low dosage

tPA dose of 2.5mg

Group Type: EXPERIMENTAL

tPA low dosage

Intervention Type: DRUG

Tissue plasminogen activator 2.5mg

Interventions

tPA standard dosage

Tissue plasminogen activator 25mg dosage

Intervention Type: DRUG

tPA low dosage

Tissue plasminogen activator 2.5mg

Intervention Type: DRUG

Other Intervention Names

tissue plasminogen activator; tissue plasminogen activator

Eligibility Criteria

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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Godfrey, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Other Identifiers

2000024040

Identifier Type: -

Identifier Source: org_study_id