Objective: To determine the feasibility and acute (i.e., within 72 hrs) safety of three levels of systolic blood pressure reduction in subjects with supratentorial intracerebral hemorrhage treated within 6 hrs after symptom onset. Design: A traditional phase I, dose-escalation, multicenter prospective study. Settings: Emergency departments and intensive care units. Patients: Patients with intracerebral hemorrhage with elevated systolic blood pressure >170 mm Hg who present to the emergency department within 6 hrs of symptom onset. Intervention: Intravenous nicardipine to reduce systolic blood pressure to a target of: (1) 170 to 200 mm Hg in the first cohort of patients; (2) 140 to 170 mm Hg in the second cohort; and (3) 110 to 140 mm Hg in the third cohort. Measurements and Main Results: Primary outcomes of interest were: (1) treatment feasibility (achieving and maintaining the systolic blood pressure goals for 18-24 hrs); (2) neurologic deterioration within 24 hrs; and (3) serious adverse events within 72 hrs. Safety stopping rules based on neurologic deterioration and serious adverse events were prespecified and approved by an NIH-appointed Data and Safety Monitoring Board, which provided oversight on subject safety. Each subject was followed-up for 3 months to preliminarily assess mortality and the clinical outcomes. A total of 18, 20, and 22 patients were enrolled in the respective three tiers of systolic blood pressure treatment goals. Overall, 9 of 60 patients had treatment failures (all in the last tier). A total of seven subjects with neurologic deterioration were observed: one (6%), two (10%), and four (18%) in tier one, two, and three, respectively. Serious adverse events were observed in one subject (5%) in tier two and in three subjects (14%) in tier three. However, the safety stopping rule was not activated in any of the tiers. Three (17%), two (10%), and five (23%) subjects in tiers one, two, and three, respectively, died within 3 months. Conclusions: The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds, and the 3-month mortality rate was lower than expected in all systolic blood pressure tiers. The results form the basis of a larger randomized trial addressing the efficacy of systolic blood pressure reduction in patients with intracerebral hemorrhage.
Bibliographical noteFunding Information:
Dr. Palesch is funded by the NIH U01 NS054630, U01 NS059041, R01 NS057127 , and R01 NS062778 , and by Boehringer-Ingelheim.
Dr. Qureshi has received funding from National Institutes of Health RO-1-NS44976-01A2 (medication provided by ESP Pharma), American Heart Association Established Investigator Award 0840053N, and Minnesota Medical Foundation, Minneapolis, MN.
- Hematoma expansion
- Intracerebral hemorrhage
- Systolic blood pressure