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

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.

Study Overview

• Status: Withdrawn
• Conditions: Pleural Effusion; Cancer, Lung
• Intervention / Treatment: Drug: tPA standard dosage; Drug: tPA low dosage

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 Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: tPA standard dosage; Tissue Plasminogen Activator (tPA) dose of 10 to 25 mg.	Drug: tPA standard dosage; Tissue plasminogen activator 25mg dosage; Other Names: tissue plasminogen activator
Experimental: tPA low dosage; tPA dose of 2.5mg	Drug: tPA low dosage; Tissue plasminogen activator 2.5mg; Other Names: tissue plasminogen activator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	up to 40 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	up to 90 days
Rate of pleurodesis	The rate of patients who are able to have the indwelling pleural catheter removed.	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.	up to 40 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup analysis of patients with trapped lung	We will also perform subgroup analysis by patients with trapped lung, stratification by primary tumor type, and stratification by the LENT score (a validated prognostic score for predicting mortality in patients with MPE).	up to 40 days

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Mark Godfrey, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: September 18, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (Actual): September 19, 2018

Study Record Updates

• Last Update Posted (Actual): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Lung Neoplasms; Pleural Effusion, Malignant; Pleural Effusion; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: 2000024040

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No