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Background: Hemodialysis catheter dysfunction (CD) is the inability to attain adequate blood pump speeds (BPS) and is attributed to thrombus or catheter malposition; alteplase (TPA) is often given in a variety of dwell times to treat CD. The purpose of this study was to determine if TPA dwell time affects short- or long-term catheter patency rates., Methods: Sixty hemodialysis (HD) patients with CD, as defined by BPS of < 250 mL/min, were randomized to receive either 1- or > 48-hr (to subsequent HD run) TPA dwell. The primary outcomes were catheter patency (BPS of > 250 mL/min) at the subsequent HD run and catheter patency at 2 weeks. The secondary outcome was the time from study entry to the next catheter intervention (including subsequent TPA installation)., Results: After TPA installation, a 78% overall catheter patency rate was observed at the subsequent HD run, falling to 48% patency at 2 weeks. There is no statistically significant difference between the short and long TPA dwell groups for catheter patency at the subsequent HD run (76.9% vs. 79.4%) or at 2 weeks (42.3% vs. 52.9%). Multivariate analysis demonstrates that the use of TPA on two or more previous occasions is a predictor of TPA failure both at the subsequent HD run and at 2 weeks. TPA installation achieves a median catheter function time of only 14 days, after which CD reoccurs., Conclusion: This study demonstrates that although patency for the next HD run can be achieved with either short or long TPA dwell, neither is reliable in terms of long-term patency. Strategies that employ TPA for CD are temporary and allow a 2-week window during which more definitive therapies for HD access should be sought.