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TNK for Loculated Pleural Effusions in Patients With Malignancy

Phase 2/Phase 3
18 Years
Not Enrolling
Pleural Effusion

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Trial Information

TNK for Loculated Pleural Effusions in Patients With Malignancy

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.

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

- Prior enrollment in the study

- Known allergy to TNK or any of its components

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Outcome 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.

Outcome Time Frame:

3-5 days

Safety Issue:


Principal Investigator

Hyo-Chun Yoon, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Kaiser Permanente


United States: Food and Drug Administration

Study ID:




Start Date:

January 2008

Completion Date:

September 2011

Related Keywords:

  • Pleural Effusion
  • pleural effusion
  • malignancy
  • loculated
  • Neoplasms
  • Pleural Effusion



Kaiser Foundation Hospital Honolulu, Hawaii  96819