Introduction: As large clinical trials for spontaneous intracerebral hemorrhage (ICH) increasingly influence management, recruitment of diverse populations must be ensured to fully understand the disease process and benefit of interventions to the general public. There is little data on sex, race and outcomes in ICH trials. We hypothesize that women and geographic minorities are underrepresented in ICH clinical trials and that there exist population specific differences in mortality, functional outcomes and response to interventions.
Methods: Pooled analysis of 5456 subjects from the following clinical trials: VISTA (985), INTERACT I (404) and II (2829), STICH II (597), MISTIE II (141) and CLEAR III (500). Patients were grouped by sex, race, and geographic location. Modified Rankin Scale [mRS] was obtained at 30 days and 3 months.
Results: More men than women participated in ICH trials (61.9% vs. 38.1%); women were older and more likely to have hypertension; men had more coronary artery disease. Women presented with lower Glasgow Coma scale, higher ICH score and more intraventricular hemorrhage. Day 90 mortality was 13.9% in women and 16.6 % in men (p=0.01); 90 day poor outcome (mRS 3-5) was 57.2% in women and 51.0% in men (p<0.001). Only mortality was significantly different between sexes after adjustment for ICH score. Race representation varied in these clinical trials: 1.5% Hispanic; 6.6% black; 14% Arabic; 31% white and 43.4% Asian. Day 90 mortality and mRS 3-5 were highest in Hispanics (22.1%, 78.3%, respectively) and lowest in Asians (9.5%, 43.8%). Hispanics had higher ICH score, but blacks and Hispanics had lower day 90 mortality compared to whites in adjusted models. Asians had both lower mortality and less day 90 mRS 3-5 vs. whites while Arabics and blacks were more likely to have day 90 mRS 3-5. Study interventions were well balanced by sex and race.
Conclusions: Sex and race representation in ICH clinical trials only partially equate to current understanding of epidemiology of ICH. There is a lack of trial evidence from Africa and South America and under-representation of women, Hispanics and blacks. Despite higher ICH severity, Hispanics had lower adjusted mortality risk while males had higher risk and Arabics and blacks had worse adjusted poor outcomes.