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10/10/2001

Alteplase Licensed for Catheter Clearance

Cheryl A. Thompson

The licensing for alteplase has been expanded to include the restoration of function to central venous access devices (CVADs), making the thrombolytic agent the first one to have FDA-approved labeling for this indication since the 1998 departure of urokinase from the market. Genentech Inc. will market Cathflo Activase in 2-mg vials for single-patient use.

The efficacy of alteplase for the new indication was shown in two clinical trials with patients who had an improperly functioning CVAD that had originally been inserted to facilitate the administration of cancer chemotherapy, total parenteral nutrition, or other medications requiring long-term use. A CVAD was defined as nonfunctioning if at least 3 mL of blood could not be withdrawn through the device. Restoration of function was defined as the ability to withdraw 3 mL of blood and infuse 5 mL of sodium chloride injection through the device.

The studies excluded patients who had a hemodialysis catheter, were known to have a mechanical occlusion in the CVAD, were at high risk for bleeding or embolization, were <2 years old, or who weighed <10 kg.

In the randomized, double-blind study of 150 patients, 67% of those who received 2 mg of a 1-mg/mL alteplase solution in the lumen of their CVAD's catheter had a functioning device 120 minutes later.1 A second alteplase treatment restored functioning of the CVAD for an additional 14% of the patients. Sixteen percent of the patients who received a placebo solution had a functioning device in 120 minutes.

The open-label study involved 995 patients and no placebo. Thirty minutes after instillation of 2 mg of a 1-mg/mL alteplase solution, 52% of the patients had a functioning CVAD; by 120 minutes, the success rate was 75%. Instillation of a second alteplase dose in 209 of the remaining dysfunctional catheters brought the total success rate to 85%.

Serious adverse events—catheter-related sepsis, major hemorrhage from a gastrointestinal source, or subclavian and upper-extremity deep-vein thrombosis—occurred in <0.5% of patients during the clinical studies. No one had an allergic-type reaction, according to the product’s labeling.

The recommended dose of alteplase for restoring function to a CVAD is 2 mg in 2 mL of solution for patients weighing >30 kg. Patients weighing >10 kg but <30 kg should receive a dose of alteplase 1-mg/mL solution equivalent to 110% of the volume of the catheter's internal lumen but not more than 2 mg. A second dose may be instilled in the catheter if it is not functioning 120 minutes after the first dose was delivered. The product’s labeling includes step-by-step instructions for instilling the first and second doses.

Cathflo Activase is provided as a lyophilized powder in single-use vials containing 2.2 mg of alteplase. Unopened vials must be stored at 2–8 degrees C. Upon reconstitution with 2.2 mL of sterile water for injection, the 1-mg/mL solution must be used within eight hours. The vials are designed to allow for the withdrawal of 2 mL of a 1-mg/mL solution when prepared according to directions.

  1. Ponec D, Irwin D, Haire W et al., for the COOL Investigators. Recombinant tissue plasminogen activator (alteplase) for restoration of flow in occluded central venous access devices: a double-blind placebo-controlled trial—the Cardiovascular thrombolytic to Open Occluded Lines (COOL) efficacy trial. J Vasc Interv Radiol. 2001; 12:951-5.