Tenecteplase (TNK) for Loculated Pleural Effusions in Patients With Malignancy
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.
Drug: normal saline
Drug: TNK (Tenecteplase)
|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|
- 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 ]
- Percentage of Patients With Hemorrhagic Complications Associated With Catheter Drainage [ Time Frame: 3-5 days ] [ Designated as safety issue: Yes ]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
- 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. [ Time Frame: 3-5 days ] [ Designated as safety issue: No ]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.
- Percentage 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 ]This measures the number of hospital days for each participant after they were started on their infusion therapy.
|Study Start Date:||January 2008|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01580618
|United States, Hawaii|
|Kaiser Foundation Hospital|
|Honolulu, Hawaii, United States, 96819|
|Principal Investigator:||Hyo-Chun Yoon, MD||Kaiser Permanente|