TROPICS 2: A Phase III, Open-Label, Single-Arm Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters.

Abstract 1074 Poster Board I-96 Introduction: For many patients, central venous catheters (CVCs) are the only option for vascular access. Thrombotic occlusion is a common complication of CVCs and can prevent delivery of treatment. The objectives of this phase III, open-label, single-arm study were to evaluate the safety and efficacy of the thrombolytic agent tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, in restoring function to occluded CVCs. Methods: Pediatric and adult subjects with dysfunctional non-hemodialysis CVCs, defined by the inability to withdraw 3 mL of blood (1 mL of blood for subjects weighing <10 kg) were eligible. Subjects received intraluminal tenecteplase at a dose of up to 2 mL (2 mg); subjects weighing <30 kg received instillations of tenecteplase equal to 110% of the internal lumen volume (maximum volume, 2 mL). Tenecteplase was allowed to dwell in the lumen for up to 120 minutes. CVC function, defined as the ability to both withdraw 3 mL of blood or fluid and infuse 5 mL of normal saline (1 mL and 3 mL, respectively, for subjects <10 kg), was assessed at 15, 30, and 120 minutes after drug instillation. If function was not restored at 120 minutes, the initial dose was withdrawn, and a second dose was instilled for up to 120 minutes. CVC assessments were repeated as for the first dose. The primary efficacy endpoint was restoration of CVC function within 120 minutes after a single administration of tenecteplase. All adverse events (AEs) were documented from instillation of the first tenecteplase dose through 48-96 hours after treatment. Targeted AEs (intracranial hemorrhage, major bleeding, embolic events, thrombosis, catheter-related bloodstream infection [CRBSI], and catheter-related complications) and study-drug–related serious AEs were recorded through 7 days after treatment. Results: Tenecteplase was administered to 246 subjects (mean age 43.6 years; range, 0-92 years), 72 (29.2%) of whom were under 17 years of age. Most subjects had a port catheter (69.5%), and the most frequent indication for catheter insertion was chemotherapy (78.0%). Most subjects (186; 75.6%) received only a single dose of tenecteplase, and 60 (24.3%) subjects required a second dose of tenecteplase. Restoration of CVC function was achieved in 177 (72.0%) subjects within 120 minutes after the first dose of tenecteplase. Following instillation of up to 2 doses of tenecteplase, CVC function was restored in 200 (81.3%) subjects, with similar restoration rates observed in pediatric (83.3%) and adult (80.5%) subjects. Among those who had treatment success and underwent catheter assessment within 7 days of treatment, 111 (81.0%) subjects maintained catheter patency. Thirty-one (12.6%) subjects experienced a treatment-emergent AE; the most common events were pyrexia (6 subjects), neutropenia (3 subjects), and nausea (2 subjects).Two targeted AEs were reported, both CRBSIs, but neither event was judged by the investigator to be related to tenecteplase; and in both cases, blood cultures were subsequently reported negative. No cases of intracranial hemorrhage, major bleeding, thrombosis, embolism, or catheter-related complications were reported. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase; however, this subject was concurrently receiving a chemotherapeutic agent, which the investigator also considered to be related to the AE. Conclusions: Serial administration of up to 2 doses of tenecteplase into CVCs is safe and effective for restoration of catheter function in pediatric and adult subjects with dysfunctional CVCs. Disclosures: Off Label Use: Tenecteplase is a thrombolytic agent under study for clearance of dysfunctional central venous catheters. Shulman: Takeda Pharmaceuticals: Research Funding; NPS Pharmaceuticals: Consultancy. Jacobs: Speaking engagements unrelated to commercial activity: Honoraria. Blaney: Genentech: Employment, Equity Ownership. Ashby: Genentech: Employment, Equity Ownership. Gillespie: Quintiles: Employment, Quintiles is a contract research organization contracted by Genentech to execute the TROPICS trials.. Begelman: Genentech: Employment, Equity Ownership.