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

Study Overview
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Brief Summary
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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.

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

Conditions
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Dysfunctional Hemodialysis Catheters

Intervention / Treatment
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* Drug: placebo
* Drug: tenecteplase


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: tenecteplase<br>* For the initial treatment, 2 mL of reconstituted lyophilized tenecteplase instilled into each lumen of the HD catheter; subsequent treatments were 2 mL of open-label tenecteplase<br>|
| Placebo Comparator: 2<br> | Drug: placebo<br>* For the initial treatment, 2 mL of placebo instilled into each lumen of the HD catheter; subsequent treatments were 2 mL of open-label tenecteplase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1 | 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. | Visit 1 of HD treatment | 
| Incidence of Targeted Adverse Events (AEs) From Initial Study Drug Administration Through the Start of Visit 2 | Targeted AEs were intracranial hemorrhages (ICHs), major bleeding, embolic events, thrombosis, catheter-related bloodstream infections (CRBSIs), and catheter related complications | Visits 1 and 2 of consecutive HD treatments | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BFR From Baseline to the End of HD at Visit 1 | BFR is measured in mL/minute. | Visit 1 of HD treatment | 
| Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Extended Dwell Tenecteplase at Visit 1) | 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. | Visit 2 of consecutive HD treatments | 
| Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Open-label Tenecteplase at Visit 2) | 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. | Visit 2 of consecutive HD treatments | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HD, Hemodialysis, Catheter clearance, TNKase, Renal Insufficiency