A Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters (TROPICS 2)

A Phase III, Open-Label, Single-Arm Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

This was a Phase III, open-label, single-arm study that was conducted at 43 centers in the United States and Canada. 251 adult and pediatric patients with dysfunctional central venous catheters (CVCs) were enrolled in the study and treated with one or two doses of tenecteplase.

Study Overview

• Status: Completed
• Conditions: Dysfunctional Central Venous Access Catheters
• Intervention / Treatment: Drug: tenecteplase

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinically stable, in the opinion of the investigator
• CVC occlusion
• Able to have fluids infused at the volume necessary to instill study drug into the CVC

Exclusion Criteria:

• Able to have 3 mL of blood (patients weighing ≥ 10 kg) or 1 mL of blood (patients weighing < 10 kg) withdrawn from the selected CVC following patient repositioning
• Selected study CVC inserted < 2 days prior to treatment
• Selected study CVC implanted specifically for hemodialysis (HD) or internally coated with any therapeutic agent
• Use of a power injector on the selected study CVC during study drug treatment
• Evidence of mechanical, non-thrombotic occlusion of the selected study CVC (e.g., kink in the catheter or suture constricting the catheter)
• Previously treated in this study or any tenecteplase catheter clearance trial
• Use of any investigational drug or therapy within 28 days prior to treatment
• Use of a fibrinolytic agent (e.g., alteplase, tenecteplase, reteplase, or urokinase) within 24 hours prior to treatment
• Known to be pregnant or breastfeeding at screening
• Known bacteremia or known or suspected infection in the CVC catheter
• Known history of intracranial hemorrhage (within the previous 3 years), intracranial aneurysm, or arteriovenous malformation
• Use of heparin (unfractionated or low molecular weight) or any other anticoagulants within 24 hours prior to treatment, except heparin used for prophylaxis or intermittent or low-dose, continuous infusion of heparin to maintain catheter or vessel patency
• Subjects treated with warfarin only: international normalized ratio (INR) ≥ 3.0 within 7 days prior to Visit 1, or a target INR range that allows for an INR ≥ 3.0
• Initiation of or increase in dose of Plavix® (clopidogrel bisulfate) within 7 days prior to treatment
• At high risk for bleeding events or embolic complications (i.e., recent pulmonary embolus, deep vein thrombosis, endarterectomy, or clinically significant right-to-left shunt) in the opinion of the investigator, or with known condition for which bleeding constitutes a significant hazard
• Known hypersensitivity to tenecteplase or any component of the formulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tenecteplase

Drug: tenecteplase; 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of tenecteplase (i.e., 2 mg of tenecteplase). Patients weighing < 30 kg received instillations of tenecteplase equal to 110% of the internal lumen volume of the dysfunctional CVC. This dose was rounded to the nearest 0.1 mL and should not have exceeded 2 mL (2 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Had Cumulative Restoration Rates of Central Venous Catheter (CVC) Function Following a Single Administration of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	120 minutes after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Single Administration of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	15 minutes after first dose
Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Single Administration of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	30 minutes after first dose
Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Second Administration of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	15 minutes after second dose
Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Second Administration of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	30 minutes after second dose
Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Second Administration of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	120 minutes after second dose
Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following Administration of One or Two Doses of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Up to 120 minutes post-treatment (Dose 1 or Dose 2)
Percentage of Patients Who Had Cumulative Restoration Rates Restoration Rates of CVC Function at Any Time During the Study and Who Maintained Catheter Patency the Next Time the Catheter Was Assessed, up to 7 Days Following the Last Dose of Tenecteplase	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Up to 7 days post-treatment

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Barbara Gillespie, M.D., FASN, Quintiles, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: November 2, 2006
• First Submitted That Met QC Criteria: November 2, 2006
• First Posted (Estimate): November 6, 2006

Study Record Updates

• Last Update Posted (Estimate): April 27, 2011
• Last Update Submitted That Met QC Criteria: March 29, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: CVA; CVAD; TNKase; Central venous access catheter
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: N3699g