STUDY OBJECTIVE: To test the hypothesis that a reduced dose of bolus recombinant human tissue-type plasminogen activator (rt-PA) (0.6 mg/kg/15 min, maximum of 50 mg) would result in fewer bleeding complications than standard 100 mg of rt-PA administered as a continuous infusion over 2 h among hemodynamically stable patients with pulmonary embolism (PE). Subsidiary objectives were to compare the two rt-PA regimens with respect to the following: (1) the rate of other adverse clinical events; (2) the magnitude of change from baseline on perfusion lung scans, pulmonary angiograms, or echocardiograms; and (3) the differences in coagulation parameters over time. DESIGN: A double-blind, double-dummy, randomized, controlled trial. SETTING:Twenty-eight participating hospitals in the United States, Italy, and Canada. PATIENTS: Patients could be included if they had symptoms or signs of PE within 14 days of presentation as well as high-probability lung scans and/or pulmonary angiograms demonstrating PE. INTERVENTIONS: Randomization was undertaken with a 2:1 allocation ratio to rt-PA 0.6 mg/kg/15 min (maximum of 50 mg) or to 100 mg/2 h. Ninety patients were randomized, and 87 patients were treated: 60 withbolus rt-PA and 27 with 2-h rt-PA. All patients underwent baseline and 20- to 28-h follow-up perfusion lung scintigraphy. Patients at angiogram centers underwent baseline and 2-h follow-up angiography, while patients at echocardiogram centers underwent baseline, 3-h, and 20- to 28-h echocardiography. Forty-eight patients also participated in an ancillary study of serial fibrinogen and fibrin degradation product levels. RESULTS: In the first 14 days after randomization, there were six deaths: five (8.3 percent) in the bolus group vs one death (3.7 percent) in the 2-h group (p = 0.66). There were two clinically suspected nonfatal recurrent PEs during the first 14 days after therapy, one in each treatment group. Overall, 14 patients suffered major or other important bleeding: 8 in the bolus group and 6 in the 2-h group (p = 0.35). Changes in efficacy parameters (scans, angiograms, or echocardiograms) were similar in the two treatment groups. After initiation of therapy, patients who had received bolus rt-PA had less depression of fibrinogen levels (p = 0.007) and smaller increases in fibrinogen degradation products (p = 0.013) than patients who had received 100 mg of rt-PA over 2 h. CONCLUSIONS: No significant differences were detected between the bolus rt-PA and 2-h rt-PA with respect to bleeding complications, adverse clinical events, or imaging studies. There was less fibrinogenolysis with the bolus dosing regimen.
RCT Entities:
STUDY OBJECTIVE: To test the hypothesis that a reduced dose of bolus recombinant humantissue-type plasminogen activator (rt-PA) (0.6 mg/kg/15 min, maximum of 50 mg) would result in fewer bleeding complications than standard 100 mg of rt-PA administered as a continuous infusion over 2 h among hemodynamically stable patients with pulmonary embolism (PE). Subsidiary objectives were to compare the two rt-PA regimens with respect to the following: (1) the rate of other adverse clinical events; (2) the magnitude of change from baseline on perfusion lung scans, pulmonary angiograms, or echocardiograms; and (3) the differences in coagulation parameters over time. DESIGN: A double-blind, double-dummy, randomized, controlled trial. SETTING: Twenty-eight participating hospitals in the United States, Italy, and Canada. PATIENTS: Patients could be included if they had symptoms or signs of PE within 14 days of presentation as well as high-probability lung scans and/or pulmonary angiograms demonstrating PE. INTERVENTIONS: Randomization was undertaken with a 2:1 allocation ratio to rt-PA 0.6 mg/kg/15 min (maximum of 50 mg) or to 100 mg/2 h. Ninety patients were randomized, and 87 patients were treated: 60 with bolus rt-PA and 27 with 2-h rt-PA. All patients underwent baseline and 20- to 28-h follow-up perfusion lung scintigraphy. Patients at angiogram centers underwent baseline and 2-h follow-up angiography, while patients at echocardiogram centers underwent baseline, 3-h, and 20- to 28-h echocardiography. Forty-eight patients also participated in an ancillary study of serial fibrinogen and fibrin degradation product levels. RESULTS: In the first 14 days after randomization, there were six deaths: five (8.3 percent) in the bolus group vs one death (3.7 percent) in the 2-h group (p = 0.66). There were two clinically suspected nonfatal recurrent PEs during the first 14 days after therapy, one in each treatment group. Overall, 14 patients suffered major or other important bleeding: 8 in the bolus group and 6 in the 2-h group (p = 0.35). Changes in efficacy parameters (scans, angiograms, or echocardiograms) were similar in the two treatment groups. After initiation of therapy, patients who had received bolus rt-PA had less depression of fibrinogen levels (p = 0.007) and smaller increases in fibrinogen degradation products (p = 0.013) than patients who had received 100 mg of rt-PA over 2 h. CONCLUSIONS: No significant differences were detected between the bolus rt-PA and 2-h rt-PA with respect to bleeding complications, adverse clinical events, or imaging studies. There was less fibrinogenolysis with the bolus dosing regimen.
Authors: Clive Kearon; Elie A Akl; Anthony J Comerota; Paolo Prandoni; Henri Bounameaux; Samuel Z Goldhaber; Michael E Nelson; Philip S Wells; Michael K Gould; Francesco Dentali; Mark Crowther; Susan R Kahn Journal: Chest Date: 2012-02 Impact factor: 9.410