Hematoma expansion shift analysis to assess acute intracerebral hemorrhage treatments

Objective: Hematoma expansion (HE) is commonly analyzed as a dichotomous
outcome in intracerebral hemorrhage (ICH) trials.  In this
proof-of-concept study, we propose a “HE shift” analysis model as a method
to improve the evaluation of candidate ICH therapies. Methods: Using data
from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II
(ATACH-2) trial, we performed HE shift analysis in response to intensive
blood pressure lowering by generating polychotomous strata based on a)
previously established HE definitions, b) percentile/absolute quartiles of
hematoma volume change, and c) quartiles of 24-hour follow-up hematoma
volumes. The relationship between blood pressure treatment and HE shift
was explored using proportional odds models. Results: The primary analysis
population included 863 patients. In both treatment groups, approximately
one-third of patients exhibited no HE. Using a trichotomous HE
stratification, the highest strata of ≥33% revealed a 5.8% reduction in
hematoma growth for those randomized to intensive therapy (aOR: 0.77 [95%
CI: 0.60-0.99]). Using percentile quartiles of hematoma volume change, we
observed a favorable shift to reduce growth in patients treated with
intensive therapy: aOR: 0.73 (0.57-0.93). Similarly, in a tetrachotomous
analysis of 24-hour follow-up hematoma volumes, shifts in the highest
stratum (> 21.9 mL) was most notable. Conclusions: Our findings
suggest that intensive blood pressure reduction may preferentially
mitigate growth in patients at risk of high volume HE. A shift analysis
model of HE provides additional insights into the biological effects of a
given therapy and may be an additional way to assess hemostatic agents in
future studies. Registration: ClinicalTrials.gov Identifier: NCT01176565