Clinical trial NCT00396032: A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dysfunctional Hemodialysis Catheters
Keywords: HD
Hemodialysis
Catheter clearance
TNKase
Renal Insufficiency
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2006-11-06
Enrollment: 150
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Subjects Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1
timeFrame: Visit 1 of HD treatment
measure: Incidence of Targeted Adverse Events (AEs) From Initial Study Drug Administration Through the Start of Visit 2
timeFrame: Visits 1 and 2 of consecutive HD treatments
Secondary outcomes:
measure: Change in BFR From Baseline to the End of HD at Visit 1
timeFrame: Visit 1 of HD treatment
measure: Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Extended Dwell Tenecteplase at Visit 1)
timeFrame: Visit 2 of consecutive HD treatments
measure: Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Open-label Tenecteplase at Visit 2)
timeFrame: Visit 2 of consecutive HD treatments
Other outcomes:
Locations:
Study officials:
name: Barbara Gillespie, M.D., FASN
role: STUDY_DIRECTOR
References:
citation: Tumlin J, Goldman J, Spiegel DM, Roer D, Ntoso KA, Blaney M, Jacobs J, Gillespie BS, Begelman SM. A phase III, randomized, double-blind, placebo-controlled study of tenecteplase for improvement of hemodialysis catheter function: TROPICS 3. Clin J Am Soc Nephrol. 2010 Apr;5(4):631-6. doi: 10.2215/CJN.06520909. Epub 2010 Feb 4.