A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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