PURPOSE: Thrombosis of central venous access devices (CVADs) is a relatively frequent complication. Alteplase (tissue plasminogen activator) has been used to salvage dysfunctional devices. The purpose of this study was to analyze the safety and efficacy of alteplase after administration of a maximum of two 2-mg/2-mL doses to thrombosed CVADs. MATERIALS AND METHODS: A combined analysis was performed of two pivotal prospective phase-III clinical trials (Cardiovascular thrombolytic to Open Occluded Lines [COOL] Trials) involving 80 centers enrolling patients from November 1999 through December 2000. Patients 2 years of age or older (with body weights >10 kg) with dysfunctional nondialysis CVADs were eligible, including those with peripherally inserted central catheters, apheresis catheters, and ports. Alteplase (2 mg/2 mL) was instilled into the lumen of the central venous catheter and allowed to dwell for as long as 120 minutes. For patients with body weights of 10-30 kg, 110% of the internal lumen volume of alteplase (2 mg/2 mL) was administered. If the device was still occluded after a maximum of 120 minutes, a second alteplase dose was given and allowed to dwell for as long as 120 minutes. The primary efficacy endpoint was designated as restored function after a maximum of two doses. The primary safety endpoint was intracranial hemorrhage (ICH) within 5 days. RESULTS: A total of 1,064 patients (465 men, 599 women; mean age, 50.7 y; range, 2-91 y) with dysfunctional catheters were treated. After alteplase administration, function was restored in 798 patients (75.0%; 95% CI: 72.3%, 77.6%) after one dose and 905 (85.1%; 95% CI: 82.8%, 87.2%) after two doses. Efficacy rates were similar among catheter types (single-, double-, and triple-lumen catheters, and ports). Serious adverse events monitored within 30 days of treatment included ICH (0.0%), embolic events (0.0%), gastrointestinal bleeding (0.3%), thrombosis (0.3%), and sepsis (0.4%). One event (fever) was attributed to the study drug. Efficacy was independent of age, sex, body weight, and catheter type. CONCLUSION: A regimen of as many as two 2-mg doses of alteplase is safe and effective for restoring flow to occluded central venous access devices.
PURPOSE:Thrombosis of central venous access devices (CVADs) is a relatively frequent complication. Alteplase (tissue plasminogen activator) has been used to salvage dysfunctional devices. The purpose of this study was to analyze the safety and efficacy of alteplase after administration of a maximum of two 2-mg/2-mL doses to thrombosed CVADs. MATERIALS AND METHODS: A combined analysis was performed of two pivotal prospective phase-III clinical trials (Cardiovascular thrombolytic to Open Occluded Lines [COOL] Trials) involving 80 centers enrolling patients from November 1999 through December 2000. Patients 2 years of age or older (with body weights >10 kg) with dysfunctional nondialysis CVADs were eligible, including those with peripherally inserted central catheters, apheresis catheters, and ports. Alteplase (2 mg/2 mL) was instilled into the lumen of the central venous catheter and allowed to dwell for as long as 120 minutes. For patients with body weights of 10-30 kg, 110% of the internal lumen volume of alteplase (2 mg/2 mL) was administered. If the device was still occluded after a maximum of 120 minutes, a second alteplase dose was given and allowed to dwell for as long as 120 minutes. The primary efficacy endpoint was designated as restored function after a maximum of two doses. The primary safety endpoint was intracranial hemorrhage (ICH) within 5 days. RESULTS: A total of 1,064 patients (465 men, 599 women; mean age, 50.7 y; range, 2-91 y) with dysfunctional catheters were treated. After alteplase administration, function was restored in 798 patients (75.0%; 95% CI: 72.3%, 77.6%) after one dose and 905 (85.1%; 95% CI: 82.8%, 87.2%) after two doses. Efficacy rates were similar among catheter types (single-, double-, and triple-lumen catheters, and ports). Serious adverse events monitored within 30 days of treatment included ICH (0.0%), embolic events (0.0%), gastrointestinal bleeding (0.3%), thrombosis (0.3%), and sepsis (0.4%). One event (fever) was attributed to the study drug. Efficacy was independent of age, sex, body weight, and catheter type. CONCLUSION: A regimen of as many as two 2-mg doses of alteplase is safe and effective for restoring flow to occluded central venous access devices.
Authors: De-Hua Chang; Kamal Mammadov; Tilman Hickethier; Jan Borggrefe; Martin Hellmich; David Maintz; Christoph Kabbasch Journal: Ther Clin Risk Manag Date: 2017-01-24 Impact factor: 2.423