Background: The Combined approach to Lysis utilizing Eptifibatide And Rt-PA in Acute Ischemic Stroke (CLEAR), CLEAR-Enhanced Regimen (CLEAR-ER) and CLEAR-Full Dose Regimen (CLEAR-FDR) trials were phase 2 trials that examined escalating doses of recombinant tissue-type plasminogen activator (rt-PA) combined with eptifibatide in acute ischemic stroke (AIS). We pooled data from these trials and compared outcomes of the escalating doses of rt-PA plus eptifibatide to rt-PA alone.
Methods: The combination arms of the CLEAR trial were: tier 1 - 0.3mg/kg of rt-PA and tier 2 - 0.45mg/kg both combined with eptifibatide 75mcg/kg bolus and 0.75mcg/kg/min for 2 hours. CLEAR-ER combined 0.6mg/kg of rt-PA and 135mcg/kg bolus of eptifibatide and 0.75mcg/kg/min for 2 hours. CLEAR-FDR combined full dose rt-PA (0.9mg/kg) and 135mcg/kg bolus of eptifibatide and 0.75mcg/kg/min for 2 hours. The control groups for both CLEAR and CLEAR-ER received full dose rt-PA only. The primary outcome was 90-day modified Rankin score (mRS) of 0-1 or return to baseline. Logistic regression was used for the analysis.
Results: A total of 247 subjects were available for analysis; 69 from the combination arm of CLEAR (29 in tier 1 and 40 in tier 2), 101 from the combination arm of CLEAR-ER, and 27 from CLEAR-FDR. Fifty rt-PA only subjects (25 from CLEAR and 25 from CLEAR-ER) served as controls. Characteristics and outcomes adjusted for age, sex, race, NIHSS and time to IV rt-PA are shown in the Table.
Conclusion: In the CLEAR trials, eptifibatide added to rt-PA showed a progressive increase in odds of a favorable outcome, without safety concerns. A phase 3 trial of full dose rt-PA plus the eptifibatide dose used in CLEAR-ER and CLEAR-FDR is warranted to establish the efficacy of the combination for improving AIS outcome.