BACKGROUND AND PURPOSE: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. METHODS: CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. RESULTS: Of 126 subjects, 101 received combination therapy, and 25 receivedstandard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). CONCLUSIONS: The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.
RCT Entities:
BACKGROUND AND PURPOSE: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. METHODS: CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic strokepatients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. RESULTS: Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). CONCLUSIONS: The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.
Authors: J P Broderick; M Lu; R Kothari; S R Levine; P D Lyden; E C Haley; T G Brott; J Grotta; B C Tilley; J R Marler; M Frankel Journal: Stroke Date: 2000-10 Impact factor: 7.914
Authors: George J Shaw; Jason M Meunier; Christopher J Lindsell; Arthur M Pancioli; Christy K Holland Journal: Thromb Res Date: 2010-09-01 Impact factor: 3.944
Authors: Mario Siebler; Michael G Hennerici; Dietmar Schneider; Gerhard M von Reutern; Rüdiger J Seitz; Joachim Röther; Otto W Witte; Gerhard Hamann; Ulrich Junghans; Arno Villringer; Jochen B Fiebach Journal: Stroke Date: 2011-08-18 Impact factor: 7.914
Authors: G Torgano; B Zecca; V Monzani; A Maestroni; P Rossi; M Cazzaniga; D Manganaro; C Boiti; E Zilioli; G Borutti; F Falaschi; C Mandelli Journal: Cerebrovasc Dis Date: 2010-01-15 Impact factor: 2.762
Authors: Harold P Adams; Mark B Effron; James Torner; Antoni Dávalos; Judith Frayne; Philip Teal; Jacques Leclerc; Barry Oemar; Lakshmi Padgett; Elliot S Barnathan; Werner Hacke Journal: Stroke Date: 2007-11-21 Impact factor: 7.914
Authors: Arthur M Pancioli; Joseph Broderick; Thomas Brott; Thomas Tomsick; Jane Khoury; Judy Bean; Gregory del Zoppo; Dawn Kleindorfer; Daniel Woo; Pooja Khatri; John Castaldo; James Frey; James Gebel; Scott Kasner; Chelsea Kidwell; Thomas Kwiatkowski; Richard Libman; Richard Mackenzie; Phillip Scott; Sidney Starkman; R Jason Thurman Journal: Stroke Date: 2008-09-04 Impact factor: 7.914
Authors: Opeolu Adeoye; Heidi Sucharew; Jane Khoury; Thomas Tomsick; Pooja Khatri; Yuko Palesch; Pamela A Schmit; Arthur M Pancioli; Joseph P Broderick Journal: Stroke Date: 2014-12-18 Impact factor: 7.914