A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters

A Phase III, Open-Label Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters

This was a Phase III, open-label study conducted at 44 centers in the United States, Canada, and Puerto Rico. 223 subjects who required hemodialysis (HD) and had a dysfunctional HD catheter were enrolled in the study.

The study consisted of four visits that corresponded to consecutive HD sessions for each patient, as well as one follow-up visit. Patients could receive up to three treatments with open-label tenecteplase during the study: one or two treatments during an initial treatment course, and eligible patients whose catheter became dysfunctional again within 21 days of the first visit received an additional treatment as part of a retreatment (RT) course.

At Visit 1, patients eligible at the beginning of HD had 2 mL (2 mg) of tenecteplase instilled into each of the two lumens of the HD catheter. After a dwell time of 1 hour, study drug was withdrawn and all subjects underwent HD. The duration of the HD session was not fixed by the study protocol, but rather by the site's HD practice, physician orders, and individual patient response during the session. Patients who did not experience treatment success at the end of Visit 1 had 2 mL (2 mg) of tenecteplase instilled into each lumen of their catheter as part of the initial treatment course. The treatment was left to dwell for an extended time, until the second HD session at Visit 2 (up to 72 hours later). Patients who received extended-dwell tenecteplase had the treatment withdrawn from their catheter at the beginning of Visit 2. Patients underwent HD as prescribed or to the extent possible.

Patients who had treatment success at Visit 1 or Visit 2 and had a recurrence of catheter dysfunction within 21 days of Visit 1 and met the re-treatment eligibility criteria had 2 mL (2 mg) of tenecteplase instilled into each lumen, followed by a 1-hour dwell time at re-treatment Visit 1.

Inclusion Criteria: for the Study

• Clinically stable, in the opinion of the investigator
• Use of a cuffed, tunneled HD catheter
• HD prescribed at a blood flow rate (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: for the Study

• 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
• 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