A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters
- Conditions
- Dysfunctional Hemodialysis Catheters
- Interventions
- Drug: placebo
- Registration Number
- NCT00396032
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This was a Phase III, randomized, double-blind, placebo-controlled study conducted at 37 centers in the United States. 150 subjects ≥ 16 years of age who required hemodialysis (HD) and had a dysfunctional HD catheter were enrolled in the study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 150
- Clinically stable, in the opinion of the investigator
- Use of a cuffed, tunneled HD catheter
- HD prescribed at a BFR of ≥300 mL/min
- Baseline BFR (at any time during the first 60 minutes of HD) of <300 mL/min at an associated pre-pump negative arterial pressure in the range between and including -240 mmHg and -280 mmHg
- Baseline BFR (at any time during the first 60 minutes of HD) at least 25 mL/min below the prescribed BFR
- Demonstrated BFR of ≥300 mL/min (using catheter lines in the customary direction) at an arterial pressure in the range of 0 to -280 mmHg in at least one HD session in the 14 days prior to Visit 1
- Anticipated use of the same catheter for at least four consecutive HD sessions, on the same type and model of HD apparatus
- Able to have fluids infused at the volume necessary to instill study drug into the HD catheter
- HD catheter with sustainable BFR of ≥300 mL/min following subject repositioning
- HD catheter inserted <2 days prior to screening
- Evidence of a mechanical, non-thrombotic cause of HD catheter dysfunction (e.g., kink in the catheter or suture constricting the catheter) or dysfunction caused by known fibrin sheath
- Use of an implantable port
- HD catheter that is internally coated with any therapeutic agent (e.g., the Decathlon™ Gold catheter)
- Anticipated use of catheter for any other type of diagnostic or therapeutic procedure (i.e., other than HD) during study drug treatment
- Previously treated in this study or any tenecteplase catheter clearance trial
- Use of any investigational drug or therapy (defined as any drug or therapy that is not FDA approved) within 28 days prior to screening
- Use of a fibrinolytic agent (e.g., alteplase, tenecteplase, reteplase, or urokinase) within 7 days prior to Visit 1
- Known to be pregnant or breastfeeding at screening or at Visit 1
- Known bacteremia or known or suspected infection in the HD catheter
- Known history of any of the following: intracranial hemorrhage (within the previous 3 years), intracranial aneurysm, or arteriovenous malformation
- Use of heparin (unfractionated or low molecular weight) or other anticoagulants (e.g., for the treatment of heparin-induced thrombocytopenia) within 24 hours prior to Visit 1, except for heparin used only during HD or for prophylaxis (e.g., heparin lock or deep vein thrombosis prophylaxis)
- 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 A laboratory test to confirm the INR must have been performed within 7 days prior to Visit 1.
- Initiation of or increase in dose of Plavix® (clopidogrel bisulfate) within 7 days prior to Visit 1
- Hemoglobin ≥12.0 g/dL if on an erythropoiesis-stimulating agent (e.g., darbepoetin or erythropoietin) and the dose of the erythropoiesis-stimulating agent has not been held or reduced per institutional policy
- 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
- BFR of <300 mL/min because of symptomatic hypotension
- Uncontrolled hypertension in the opinion of the investigator
- Known hypersensitivity to tenecteplase or any component of the formulation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 placebo - 1 tenecteplase -
- Primary Outcome Measures
Name Time Method Percentage of Subjects Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1 Visit 1 of HD treatment Treatment success is defined as BFR of ≥300 mL/min and an increase from baseline BFR of ≥25 mL/min at an associated target arterial pressure in the range of 0 to -280 mmHg 30 (±10) minutes prior to the end of HD and at the end of HD.
Incidence of Targeted Adverse Events (AEs) From Initial Study Drug Administration Through the Start of Visit 2 Visits 1 and 2 of consecutive HD treatments Targeted AEs were intracranial hemorrhages (ICHs), major bleeding, embolic events, thrombosis, catheter-related bloodstream infections (CRBSIs), and catheter related complications
- Secondary Outcome Measures
Name Time Method Change in BFR From Baseline to the End of HD at Visit 1 Visit 1 of HD treatment BFR is measured in mL/minute.
Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Extended Dwell Tenecteplase at Visit 1) Visit 2 of consecutive HD treatments Treatment success is defined as BFR of ≥300 mL/min and an increase from baseline BFR of ≥25 mL/min at an associated target arterial pressure in the range of 0 to -280 mmHg 30 (±10) minutes prior to the end of HD and at the end of HD.
Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Open-label Tenecteplase at Visit 2) Visit 2 of consecutive HD treatments Treatment success is defined as BFR of ≥300 mL/min and an increase from baseline BFR of ≥25 mL/min at an associated target arterial pressure in the range of 0 to -280 mmHg 30 (±10) minutes prior to the end of HD and at the end of HD.