A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters
Condition: Dysfunctional Hemodialysis Catheters
Intervention: Tenecteplase
Intervention description: 2 mL (2 mg) of reconstituted lyophilized tenecteplase instilled into each lumen of the HD catheter.
Intervention MeSH terms: Tenecteplase
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 223.0
Sex: All
Healthy volunteers: No
Keywords: HD; TNKase; Hemodialysis; Catheter clearance

Summary:

      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.
    

Eligibility criteria:

        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