Tenecteplase (TNK) for Loculated Pleural Effusions in Patients With Malignancy

This study has been terminated.
(Unable to accrue patients at a reasonable rate)
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Hyo-Chun Yoon, Kaiser Permanente
ClinicalTrials.gov Identifier:
NCT01580618
First received: September 17, 2010
Last updated: April 18, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Pleural Effusion
Drug: normal saline
Drug: TNK (Tenecteplase)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: TNK for Loculated Pleural Effusions in Patients With Malignancy

Resource links provided by NLM:


Further study details as provided by Kaiser Permanente:

Primary Outcome Measures:
  • 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. [ Time Frame: 3-5 days ] [ Designated as safety issue: No ]
  • Hemorrhagic complications associated with catheter drainage [ Time Frame: 3-5 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percent of patients who fail initial therapy (TNK or saline) who achieve satisfactory drainage after switching to the alternative (saline or TNK) therapy. [ Time Frame: 3-5 days ] [ Designated as safety issue: No ]
  • Percent of patients able to undergo pleurodesis to prevent recurrent pleural effusion. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Duration of hospital stay from the time of initiation of infusion therapy for the loculated effusion [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: January 2008
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Normal Saline
Loculated pleural effusion infused with normal saline twice a day for three days.
Drug: normal saline
Injection of 60 ml normal saline twice a day for three days using the existing chest tube.
Active Comparator: TNKase
Loculated pleural effusion infused with TNK twice a day for three days.
Drug: TNK (Tenecteplase)
Injection of 4 mg of TNK with 59 ml normal saline into the existing chest tube twice a day for three days.
Other Name: TNKase, tenecteplase

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01580618

Locations
United States, Hawaii
Kaiser Foundation Hospital
Honolulu, Hawaii, United States, 96819
Sponsors and Collaborators
Kaiser Permanente
Genentech
Investigators
Principal Investigator: Hyo-Chun Yoon, MD Kaiser Permanente
  More Information

No publications provided

Responsible Party: Hyo-Chun Yoon, Staff Radiologist, Kaiser Permanente
ClinicalTrials.gov Identifier: NCT01580618     History of Changes
Other Study ID Numbers: HI-07HYoon-02
Study First Received: September 17, 2010
Last Updated: April 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Kaiser Permanente:
pleural effusion
malignancy
loculated

Additional relevant MeSH terms:
Neoplasms
Pleural Effusion
Pleural Diseases
Respiratory Tract Diseases
Tenecteplase
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on August 28, 2014