The beta-hCG+erythropoietin in acute stroke (BETAS) study: a 3-center, single-dose, open-label, noncontrolled, phase IIa safety trial

Abstract

Background and purpose: Animal data suggest the use of beta-human chorionic gonadotropin followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy through a 3-center, single-dose, open-label, noncontrolled, Phase IIa trial.

Methods: Patients with ischemic stroke 24 to 48 hours old and National Institutes of Health Stroke Scale score of 6 to 24 started a 9-day course of beta-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation). This study also evaluated performance of serially measured domain-specific end points.

Results: A total of 15 patients were enrolled. Two deaths occurred, neither related to study medications. No safety concerns were noted among clinical or laboratory measures, including screening for deep vein thrombosis and serial measures of serum hemoglobin. In several instances, domain-specific end points provided greater insight into impairments as compared with global outcome measures.

Conclusions: Results support the safety of this sequential, 2-growth factor therapy initiated 24 to 48 hours after stroke onset.

Figure 1

Study design

Figure 2

Hematological changes in association with B-E therapy. In parallel with B-E therapy, serum hemoglobin and reticulocyte count (mean ± SEM) showed no change over time, as the main effect of time was not significant in repeated measures ANOVA. Note that the initial increase in reticulocyte count from baseline to day 6 preceded EPO administration, and that the normal upper limit for reticulocyte count is 2.5%.