TAMPA, Fla.—Tenecteplase, a thrombolytic agent, may significantly improve the function of hemodialysis (HD) catheters blocked by blood clots, according to data from a phase 3 open-label trial.
“It is tremendously promising,” said study investigator Steven Fishbane, MD, Chief of Nephrology at Winthrop University Hospital in Mineola, N.Y. “Clotting has been a big problem. This gives us the first opportunity to help. This agent is a very important development. There are currently no FDA approved agents [for clearing HD catheter clots] so this could become the first approved drug for this purpose.”
Tenecteplase is a recombinant fibrin-specific plasminogen activator and is currently under FDA review. It is derived from tissue plasminogen activator, with modifications at three sites of the protein structure.
Tenecteplase binds to the fibrin component of the thrombus and selectively converts thrombus-bound plasminogen to plasmin. This subsequently degrades the fibrin matrix of the thrombus. The agent is indicated as a thrombolytic therapy for the acute phase of myocardial infarction (MI) for reduction of mortality associated with acute MI.
Dr. Fishbane and his colleagues conducted a study with 223 patients to determine the safety and efficacy of tenecteplase for the treatment of dysfunctional HD catheters. The mean age of the patients was 61 years (range 16-97 years). Patients with cuffed, tunneled HD catheters and a blood flow rate (BFR) of less than 300 mL/min at an arterial pressure of -240 to -280 mm Hg received 2 mg/2 mL of tenecteplase in each lumen for a one hour intracatheter dwell.
The investigators defined treatment success as achieve a BFR of 300 mL/min or greater with a 25 mL/min or greater increase from baseline BFR, without line reversal, at 30 minutes prior to HD and at the end of HD. Patients who did not achieve treatment success at the end of the initial visit received another 2 mg of tenecteplase. This second dose was given for an extended dwell period of up to 72 hours. The primary efficacy end point was the proportion of patients with treatment success at the end of the first HD visit.
Following the one hour tenecteplase dwell, 76 patients (34%) achieved treatment success, with a mean standard deviation increase from baseline BFR of 82 mL/min. Of the 116 patients who received extended-dwell tenecteplase, 57 (49%) had treatment success at the end of the next HD session, with a mean standard deviation increase from baseline BFR of 117 mL/min.
“About 20% of hemodialysis patients use catheters for dialysis and there is a large amount of dysfunction with them,” said Dr. Fishbane, who presented study findings here at the Society of Interventional Radiology annual meeting. “They are very, very prone to blood clots that form in and around the catheter.”
Tenecteplase literally lyses these clots, he added, noting that tenecteplase could decrease morbidity and improve patient satisfaction. “It certainly may improve the efficiency of dialysis and it could mean a considerable cost savings by eliminating these complications.”
Five catheter-related bloodstream infections and one thrombus occurred in the study population. All of these problems resolved with treatment. The researchers observed no episodes of intracranial hemorrhage, major bleeding, or embolic events.
“It had an excellent safety profile,” Dr. Fishbane told Renal & Urology News. “There were very few complications, mostly what would typically be expected in a hemodialysis population. Bleeding is usually the concern with lytic agents, and the good news from this study was that this type of complication was not found.”