A Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

Study Overview
=================
Brief Summary
-----------------
This was a Phase III, randomized, double-blind, placebo-controlled study that was conducted at 24 centers in the United States and Canada. 100 adult and pediatric patients with dysfunctional central venous catheters (CVCs) were randomly assigned in a 1:1 ratio to receive an initial dose of either placebo (Arm A) or tenecteplase (Arm B).

Official Title
-----------------
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

Conditions
-----------------
Dysfunctional Central Venous Access Catheters

Intervention / Treatment
-----------------
* Drug: placebo
* Drug: tenecteplase


Participation Criteria
=================
Eligibility Criteria
-----------------
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 10 kg) withdrawn from the selected study CVC following patient repositioning Selected study CVC inserted < 2 days prior to treatment Selected study CVC known to be dysfunctional for > 7 days Selected study CVC implanted specifically for hemodialysis (HD) Use of a power injector on the selected study CVC during the study 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 CVC with known or suspected infection History of any intracranial hemorrhage, aneurysm, or arteriovenous malformation Use of heparin (unfractionated or low molecular weight) within 24 hours prior to treatment, except for use of intermittent or low-dose, continuous infusion of heparin to maintain catheter or vessel patency Use of warfarin within 7 days prior to treatment, except for low-dose warfarin used for prophylaxis 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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Tenecteplase + Tenecteplase (PTT)<br> | Drug: placebo<br>* 2 mL of placebo instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of placebo). Patients weighing < 30 kg received instillations of study drug 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).<br>Drug: tenecteplase<br>* 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of tenecteplase). Patients weighing < 30 kg received instillations of study drug 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).<br>|
| Experimental: Tenecteplase + Tenecteplase + Placebo (TTP)<br> | Drug: placebo<br>* 2 mL of placebo instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of placebo). Patients weighing < 30 kg received instillations of study drug 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).<br>Drug: tenecteplase<br>* 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of tenecteplase). Patients weighing < 30 kg received instillations of study drug 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).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Had Restoration of Central Venous Catheter (CVC) Function Following a Single Administration of Study Drug | Restoration of CVC function was defined as 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 Restoration of CVC Function Following a Single Administration of Study Drug | Restoration of CVC function was defined as 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 Restoration of CVC Function Following a Single Administration of Study Drug | Restoration of CVC function was defined as 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 Restoration of CVC Function Following a Second Administration of Study Drug | Restoration of CVC function was defined as 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 Restoration of CVC Function Following a Second Administration of Study Drug | Restoration of CVC function was defined as 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 Restoration of CVC Function Following a Second Administration of Study Drug | Restoration of CVC function was defined as 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 Restoration of CVC Function Following a Third Administration of Study Drug | Restoration of CVC function was defined as 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 third dose | 
| Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | Restoration of CVC function was defined as 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 third dose | 
| Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | Restoration of CVC function was defined as 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 third dose | 
| Percentage of Patients Who Had Restoration 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 | 
| Percentage of Patients Who Had Restoration 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TNKase, CVA, CVAD, Central venous access catheter, CVA catheter