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

PURPOSE: Central venous access devices (CVADs) are a mainstay of current me dical therapy but often become occluded by thrombus. Tissue plasminogen act ivator (alteplase), at a dose of 2 mg per 2 mL, has been shown to be effect ive in restoring flow to catheters proven by radiographic contrast injectio n to be occluded by thrombus. The purpose of this double-blind placebo-cont rolled multicenter trial was to determine the efficacy of alteplase in occl uded catheters without earlier contrast injections or radiographic examinat ions. MATERIALS AND METHODS: Patients were eligible for inclusion if blood could not be withdrawn from their catheter after a period of normal function of a t least 48 hours. Single or multiple catheters, peripherally inserted centr al catheters, catheters with valves, and implanted ports were eligible; cat heters used for hemodialysis were not included. Patients were randomly assi gned to one of two groups. In one group, patients received a first dose of 2 mg alteplase followed, if needed, by a second dose of 2 mg alteplase and a third dose of placebo. The other group received placebo first followed by one 2-mg dose of alteplase and then a second, if needed. Each dose was all owed to dwell for 2 hours and ability to withdraw blood from the catheter w as reassessed. The endpoint was restoration of the ability to withdraw and infuse through the catheter. One hundred forty-nine patients were randomize d: 74 received placebo first, 75 received alteplase first. RESULTS: After the first 2-hour treatment, function was restored to 74% in the alteplase arm and 17% in the placebo arm (P < .0001 compared to placebo ). After one or two treatments, function was restored in 90% of patients. T here were no serious study-drug-related adverse events, no intracranial hem orrhage, no major hemorrhage, and no embolic events. CONCLUSION: Infusion of alteplase appeared to be safe and effective in rest oring flow to occluded catheters without need for pretreatment radiographic evaluation.