TROPICS 1: A Phase III, Randomized, Double-blind, Placebo-controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

• Published in: Journal of vascular and interventional radiology Vol. 21; no. 12; pp. 1852 - 1858
• Main Authors: Gabrail, Nashat, MD, Sandler, Eric, MD, Charu, Veena, MD, Anas, Nick, MD, Lim, Eduardo, MD, Blaney, Martha, PharmD, Ashby, Mark, PhD, Gillespie, Barbara S., MD, Begelman, Susan M., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2010
• Subjects: Adolescent; Adult; Aged; Catheterization, Central Venous - adverse effects; Catheterization, Central Venous - instrumentation; Catheters, Indwelling - adverse effects; Chi-Square Distribution; Double-Blind Method; Female; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - adverse effects; Humans; Male; Middle Aged; Placebo Effect; Radiology; Regional Blood Flow; Thrombolytic Therapy - adverse effects; Thrombosis - drug therapy; Thrombosis - etiology; Thrombosis - physiopathology; Time Factors; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - adverse effects; Treatment Outcome; United States; Young Adult; DVT; AE; CI; adverse event; central venous catheter; TNK-TNK-PBO; ICH; catheter-related bloodstream infection; CVC; placebo, tenecteplase, and tenecteplase; deep vein thrombosis; PBO-TNK-TNK; intracranial hemorrhage; MITT; confidence interval; modified intent-to-treat; CRBSI; tenecteplase, tenecteplase, and placebo
• ISSN: 1051-0443; 1535-7732
• DOI: 10.1016/j.jvir.2010.09.002

Purpose To evaluate the efficacy and safety of the thrombolytic tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, for restoring function to dysfunctional central venous catheters (CVCs). Materials and Methods In this double-blind, placebo-controlled study, eligible patients with dysfunctional nonhemodialysis CVCs were randomly assigned to two treatment arms. In the first arm (TNK-TNK-PBO), patients received an initial dose of intraluminal tenecteplase (TNK) (up to 2 mg), a second dose of tenecteplase if indicated, and a third placebo (PBO) dose. In the PBO-TNK-TNK arm, placebo was instilled first followed by up to two doses of tenecteplase, if needed, for restoration of catheter function. After administration of each dose, CVC function was assessed at 15, 30, and 120 minutes. Results There were 97 patients who received either TNK-TNK-PBO ( n = 50) or PBO-TNK-TNK ( n = 47). Within 120 minutes of initial study drug instillation, catheter function was restored to 30 patients (60%) in the TNK-TNK-PBO arm and 11 patients (23%) in the PBO-TNK-TNK arm, for a treatment difference of 37 percentage points (95% confidence interval 18–55; P = .0002). Cumulative restoration rates for CVC function increased to 87% after the second dose of tenecteplase in both study arms combined. Two patients developed a deep vein thrombosis (DVT) after exposure to tenecteplase; one DVT was considered to be drug related. No cases of intracranial hemorrhage, major bleeding, embolic events, catheter-related bloodstream infections, or catheter-related complications were reported. Conclusions Tenecteplase was efficacious for restoration of catheter function in these study patients with dysfunctional CVCs.