Clinical trial NCT01580618: Tenecteplase (TNK) for Loculated Pleural Effusions in Patients With Malignancy
Official title: TNK for Loculated Pleural Effusions in Patients With Malignancy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Pleural Effusion
Keywords: pleural effusion
malignancy
loculated
Lead sponsor: Kaiser Permanente
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2012-04-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to determine the safety and efficacy of TNK infusion for the treatment of loculated pleural effusions in patients with known malignancy compared to normal saline infusion.

Detailed description: The design of the trial will be as a single-center, prospective, blinded, randomized trial comparing the infusion of TNKase versus saline for treatment of symptomatic loculated pleural effusion in patients with malignancy. Patients with known malignancy and symptomatic loculated pleural effusion who are referred for percutaneous drainage will be eligible for this study. Patients will undergo standard placement of a 8-10 french percutaneous drain into their pleural space under computed tomography or ultrasound guidance. If there is incomplete drainage of the pleural fluid at the time of initial catheter placement or if followup chest radiography performed within 24-48 hours of chest tube placement reveals persistent pleural fluid, the effusion will be considered to be loculated. After informed consent, patients will be alternately randomized to a 3 day course of twice a day intrapleural TNKase or sterile saline injections. Both the patient and the patient's primary care physician will be blinded as to the infusate. The test fluid will be kept with the pleural space for a minimum of 2 hrs before the drainage tube is returned to suction. The standard dose of TNKase will be 4 mg/60 ml NS. The control group will received 60 ml NS for each infusion. There will be a cross-over design so that patients who fail to have significant drainage during the first 2 days of therapy may be switched to the other infusate for up to an additional three days (at the primary care provider's discretion). Thus, patients who are in the saline arm will be switched to TNKase if there is a symptomatic persistent residual loculated effusion and those who fail TNKase will be switched to saline after 2 days. This is necessary in order for primary care providers to allow their patients to be enrolled in this study since our standard of care is to use Activase. We will use a cutoff of 2 days rather than 3 days before switching therapy because we cannot justify the expense of keeping patients hospitalized for an extra day in the face of failed therapy given the extremely high cost of hospitalization. Therefore, if patients have not had significant drainage in the first 2 days of therapy with either agent (saline or TNKase), the primary care provider may request that the patient be crossed over to the other agent. However, if there is some, albeit incomplete, drainage in the first 2 days of therapy, we will ask the primary care provider to wait until a complete course of intrapleural injections has been performed. We expect to enroll 40 patients during a period of 18 months.

Eligibility criteria: Inclusion Criteria:

* Ability to provide written informed consent and comply with study assessments for the full duration of the study.
* Age \> 18 years
* Adult, non-gravid patients with malignancy and symptomatic loculated pleural effusion who has undergone percutaneous drainage will be eligible to participate. A loculated effusion is defined as an effusion whose contents cannot be completely drained at the time of initial catheter placement as documented by the initial imaging guided procedure or within 48 hours of catheter placement by chest radiography. Malignant cells need not be found within the pleural fluid.

Exclusion Criteria:

* Active internal bleeding, involving intracranial and retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts
* History of stroke within 3 months
* Intracranial neoplasm, arteriovenous malformation, or aneurysm.
* Uncorrectable bleeding diathesis (INR \> 1.5 despite therapy)
* Recent intracranial or intraspinal surgery or trauma
* Pregnancy (positive pregnancy test)
* Severe uncontrolled hypertension
* Documented empyema
* Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
* Participation in another simultaneous medical investigation or trial
* Participation in another clinical investigation within previous 30 days of catheter placement
* Prior enrollment in the study
* Known allergy to TNK or any of its components

Primary outcomes:
measure: Percentage of Patients Achieving Complete or Near Complete Drainage of Loculated Pleural Effusion as Determined From Chest Radiography After Three Days or Five Days of Intrapleural Therapy.
timeFrame: 3-5 days
measure: Percentage of Patients With Hemorrhagic Complications Associated With Catheter Drainage
timeFrame: 3-5 days
Secondary outcomes:
measure: Percentage of Patients Who Fail Initial Therapy (TNK or Saline) Who at the Request of the Hospital-based Doctor Are Then Switched to the Other Arm/Group AND Who Then Achieve Satisfactory Drainage (Saline or TNK) Therapy.
timeFrame: 3-5 days
measure: Percentage of Patients Able to Undergo Pleurodesis to Prevent Recurrent Pleural Effusion.
timeFrame: 30 days
measure: Duration of Hospital Stay From the Time of Initiation of Infusion Therapy for the Loculated Effusion
timeFrame: 30 days
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Kaiser Foundation Hospital
state: Hawaii
Study officials:
affiliation: Kaiser Permanente
name: Hyo-Chun Yoon, MD
role: PRINCIPAL_INVESTIGATOR
References: