TROPICS 1: a phase III, randomized, double-blind, placebo-controlled study of tenecteplase for restoration of function in dysfunctional central venous catheters.
OBJECTIVE
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).


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.
Gabrail Cancer Center, Canton, OH 44718, USA. ngabrailmd@aol.com
Nashat
N
Gabrail
Eric
E
Sandler
Veena
V
Charu
Nick
N
Anas
Eduardo
E
Lim
Martha
M
Blaney
Mark
M
Ashby
Barbara S
BS
Gillespie
Susan M
SM
Begelman
D000293:Adolescent; D000328:Adult; D000368:Aged; D002405:Catheterization, Central Venous / Q000009:adverse effects* / Q000295:instrumentation; D002408:Catheters, Indwelling / Q000009:adverse effects*; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D012039:Regional Blood Flow; D000077785:Tenecteplase; D015912:Thrombolytic Therapy / Q000009:adverse effects; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase