Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): Rationale and Design

Abstract

This trial is a multicenter open-labeled pilot trial to determine the tolerability and safety of three escalating levels of antihypertensive treatment goals for acute hypertension in 60 subjects with supratentorial intracerebral hemorrhage (ICH). The pilot trial is the natural development of numerous case series evaluating the effect of antihypertensive treatment of acute hypertension in subjects with ICH. The proposed trial will have important public health implications by providing necessary information for a definitive phase III study regarding the efficacy of antihypertensive treatment of acute hypertension in subjects with ICH. The specific aims of the present pilot study are to: (1) Determine the tolerability of the treatment as assessed by achieving and maintaining three different systolic blood pressure goals with intravenous nicardipine infusion for 18 to 24 hours postictus in subjects with ICH who present within 6 hours of symptom onset; (2) Define the safety, assessed by the rate of neurological deterioration during treatment and serious adverse events, of three escalating systolic blood pressure treatment goals using intravenous nicardipine infusion; and (3) Obtain preliminary estimates of the treatment effect using the rate of hematoma expansion (within 24 hours) and modified Rankin scale and Barthel index at 3 months following symptom onset.

Treatment Targets in Intracerebral Hemorrhage

“…Cohorts 2 and 3 had a trend toward worse outcome and more numerical deaths than cohort 1; however, the study was not powered to show an effect on death and disability. Consistent with findings from INTERACT, the study demonstrated that rapid blood pressure reduction was safe and feasible [68]. The ATACH-II trial, which is the next phase of ATACH, is a phase 3, randomized efficacy study designed to evaluate the therapeutic benefit of intensive acute blood pressure treatment (systolic blood pressure ≤140 mmHg) with intravenous nicardipine within 3 h of symptom onset compared with standard care (systolic blood pressure ≤180 mmHg).…”

Prevalence of elevated blood pressure in 563704 adult patients with stroke presenting to the ED in the United States

“…Elevated blood pressure is highly prevalent across different stroke subtypes. These data provide further support for planning clinical studies that address the management of elevated blood pressure and clinical outcomes in patients with acute stroke [37][38][39]. …”

Nationwide survey of antihypertensive treatment for acute intracerebral hemorrhage in Japan

“…Our observational study of 244 patients with ICH showed that lowering SBP to o138 mm Hg during the initial 24 h after admission seems to predict a favorable early outcome. 21 Two major clinical trials are ongoing to determine the safety and efficacy of intensively lowering BP for acute ICH: the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) 22 and the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH). 23 The vanguard phase of INTERACT showed that early intensive lowering of BP with a targeted SBP of 140 mm Hg and careful monitoring was feasible, safe and might have modestly attenuated hematoma growth in 346 randomized patients in the standard best practice stroke unit care.…”

“…23 The vanguard phase of INTERACT showed that early intensive lowering of BP with a targeted SBP of 140 mm Hg and careful monitoring was feasible, safe and might have modestly attenuated hematoma growth in 346 randomized patients in the standard best practice stroke unit care. 22 Phase I of ATACH investigated the potential consequences of controlling BP with i.v. nicardipine at the sequential levels of 170-200, 140-170 and 110-140 mm Hg in 60 patients.…”

“…23 The result was announced in a recent conference. 22 This survey clarified a contradiction regarding the prevalence of nicardipine administration to Japanese patients with ICH regardless of the following contraindications described on the official label; 'nicardipine is contraindicated for (I) ICH patients with a suspicion of ongoing intracranial bleeding not to enhance bleeding and for (II) acute stroke patients with elevated intracranial pressure not to accelerate intracranial pressure elevation.' When nicardipine was originally approved for commercial use as an ameliorant of cerebral circulation, not as an antihypertensive agent, in Japan in 1981, a description of the above contraindications was listed on the label following that of another ameliorant of cerebral circulation.…”