Background: The Phase 2 Combined approach to Lysis utilizing Eptifibatide And Rt-PA in Acute Ischemic Stroke - Full Dose Regimen (CLEAR-FDR) trial was a single arm trial that demonstrated the safety of full dose (0.9mg/kg) rt-PA plus eptifibatide in AIS patients treated with rt-PA within three hours of symptom onset. Interventional Management of Stroke (IMS) III randomized AIS patients to rt-PA plus endovascular therapy versus standard r-tPA. Albumin in Acute Stroke (ALIAS) Part 2 randomized patients to albumin±rt-PA versus saline±rt-PA. We compared outcomes in CLEAR-FDR patients to propensity score-matched rt-PA only subjects in ALIAS Part 2 and IMS.
Methods: All datasets were restricted to subjects with baseline modified Rankin score (mRS) of 0 or 1. Controls were selected using propensity score matching of CLEAR-FDR subjects and rt-PA only subjects from both IMS III and ALIAS. Age, gender, race, baseline mRS, baseline NIHSS score, and time from stroke onset to rt-PA were included in the logistic model used to generate a propensity score for each subject. The greedy matching algorithm was then used to match 1:3. The primary outcome was 90-day severity-adjusted mRS dichotomization based on baseline NIHSS. Secondary outcomes were 90-day mRS dichotomized as excellent (mRS 0-1); favorable (mRS 0-2); and, nonparametric analysis of the ordinal mRS.
Results: Eighteen CLEAR-FDR subjects were matched with 52 controls. Median age in CLEAR-FDR and control subjects was 67 and 68 years respectively. Median NIHSS in both CLEAR-FDR and control subjects was 11. At 90 days, CLEAR-FDR subjects had a nonsignificant greater proportion of patients with a favorable primary outcome (61% versus 38%; unadjusted RR 1.59; 95%CI 0.96-2.63; P=0.10). Secondary outcomes also favored CLEAR-FDR subjects: excellent outcomes - 67% versus 38% (RR 1.73; 95%CI 1.08-2.79; P=0.04); favorable outcomes - 67% versus 58% (RR 1.16; 95%CI 0.77-1.73; P=0.50); and ordinal Cochran-Mantel-Haenszel, P=0.13.
Conclusion: The outcomes for combination of full dose rt-PA plus eptifibatide showed a consistent direction of effect in favor of the combination over rt-PA alone. A trial to establish the efficacy of rt-PA plus eptifibatide for improving AIS outcomes is warranted and in the planning stages.