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

Pleural Effusion Clinical Trial

Official title:

TNK for Loculated Pleural Effusions in Patients With Malignancy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01580618
• Other study ID #: HI-07HYoon-02
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: September 17, 2010
• Last updated: January 2, 2015
• Start date: January 2008
• Est. completion date: September 2011

Study information

• Verified date: January 2015
• Source: Kaiser Permanente
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Pleural Effusion

Intervention

Drug:
• normal saline
Injection of 60 ml normal saline twice a day for three days using the existing chest tube.
• TNK (Tenecteplase)
Injection of 4 mg of TNK with 59 ml normal saline into the existing chest tube twice a day for three days.

Locations

Country	Name	City	State
United States	Kaiser Foundation Hospital	Honolulu	Hawaii

Sponsors (2)

Lead Sponsor	Collaborator
Kaiser Permanente	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		3-5 days	No
Primary	Percentage of Patients With Hemorrhagic Complications Associated With Catheter Drainage	This is the percentage of patients in each arm of the study (Normal saline or TNKase) who suffered a hemorrhagic complication directly associated with instillation of normal saline or TNKase	3-5 days	Yes
Secondary	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.	Only one patient who was on normal saline arm/group was switched (by request of the referring hospital-based doctor) to TNKase, but did not have complete clearing of their effusion. No patient in the TNKase arm/group was switched to normal saline. Therefore, we have removed the TNKase arm/group from this portion of the analysis since there are no participants in this group to analyze this outcome measure.	3-5 days	No
Secondary	Percentage of Patients Able to Undergo Pleurodesis to Prevent Recurrent Pleural Effusion.		30 days	No
Secondary	Duration of Hospital Stay From the Time of Initiation of Infusion Therapy for the Loculated Effusion	This measures the number of hospital days for each participant after they were started on their infusion therapy.	30 days	No