A phase III, randomized, double-blind, placebo-controlled study of tenecteplase for improvement of hemodialysis catheter function: TROPICS 3.
OBJECTIVE
Despite widespread use of tunneled hemodialysis (HD) catheters, their utility is limited by the development of thrombotic complications. To address this problem, this study investigated whether the thrombolytic agent tenecteplase can restore blood flow rates (BFRs) in dysfunctional HD catheters.


METHODS
In this randomized, double-blind study, patients with dysfunctional tunneled HD catheters, defined as a BFR <300 ml/min at -250 mmHg pressure in the arterial line, received 1-hour intracatheter dwell with tenecteplase (2 mg) or placebo. The primary endpoint was the percentage of patients with BFR > or =300 ml/min and an increase of > or =25 ml/min above baseline 30 minutes before and at the end of HD. Safety endpoints included the incidence of hemorrhagic, thrombotic, and infectious complications.


RESULTS
Eligible patients (n = 149) were treated with tenecteplase (n = 74) or placebo (n = 75). Mean baseline BFR was similar for the tenecteplase and placebo groups at 151 and 137 ml/min, respectively. After a 1-hour dwell, 22% of patients in the tenecteplase group had functional catheters compared with 5% among placebo controls (P = 0.004). At the end of dialysis, mean change in BFR was 47 ml/min in the tenecteplase group versus 12 ml/min in the placebo group (P = 0.008). Four catheter-related bloodstream infections (one tenecteplase, three placebo) and one thrombosis (tenecteplase) were observed. There were no reports of intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications.


CONCLUSIONS
Tenecteplase improved HD catheter function and had a favorable safety profile compared with placebo.
Department of Internal Medicine, Division of Nephrology, University of Tennessee College of Medicine in Chattanooga, Director, Southeast Renal Research Institute, 2300 East Third Street, Suite 100, Chattanooga, TN 37404, USA. JamesTumlinMD@Nephassociates.com
James
J
Tumlin
Jesse
J
Goldman
David M
DM
Spiegel
David
D
Roer
K Adu
KA
Ntoso
Martha
M
Blaney
Joan
J
Jacobs
Barbara S
BS
Gillespie
Susan M
SM
Begelman
D000293:Adolescent; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D002405:Catheterization, Central Venous / Q000009:adverse effects / Q000295:instrumentation*; D002406:Catheterization, Peripheral / Q000009:adverse effects / Q000295:instrumentation*; D002408:Catheters, Indwelling / Q000009:adverse effects; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow; D006435:Renal Dialysis / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods; D000077785:Tenecteplase; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase