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

• ClinicalTrials.gov Identifier: NCT03678090
• Recruitment Status: Withdrawn
• First Posted: September 19, 2018
• Last Update Posted: March 5, 2020
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

The safety and efficacy of fibrinolysis in patients with an indwelling pleural catheter for multi-loculated malignant pleural effusion.

Condition or disease	Intervention/treatment	Phase
Pleural Effusion; Cancer, Lung	Drug: tPA standard dosage; Drug: tPA low dosage	Phase 2

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Masking Description: double blinded
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: December 1, 2018
• Actual Primary Completion Date: February 28, 2020
• Actual Study Completion Date: February 28, 2020

Arms and Interventions

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 Name: tissue plasminogen activator
Experimental: tPA low dosage; tPA dose of 2.5mg	Drug: tPA low dosage; Tissue plasminogen activator 2.5mg; Other Name: tissue plasminogen activator

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Secondary Outcome Measures :

1. Time to recurrent loculation [ Time Frame: 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
2. Rate of pleurodesis [ Time Frame: up to 90 days ]
   The rate of patients who are able to have the indwelling pleural catheter removed.
3. Improvements in dyspnea using the modified Borg scale [ Time Frame: 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.

Other Outcome Measures:

1. Subgroup analysis of patients with trapped lung [ Time Frame: up to 40 days ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Sponsors and Collaborators

Yale University

Investigators

• Principal Investigator: Mark Godfrey, MD; Yale University

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT03678090
• Other Study ID Numbers: 2000024040
• First Posted: September 19, 2018
• Last Update Posted: March 5, 2020
• Last Verified: March 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pleural Effusion, Malignant; Lung Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases; Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Plasminogen; Tissue Plasminogen Activator; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action