Rationale: Management of blood pressure (BP) in the acute phase of intracerebral hemorrhage (ICH) remains controversial. Although it has been established that there is a transient moderate reduction of perihematoma cerebral blood flow (CBF) in acute ICH, the effect of BP treatment is unknown. The potential for exacerbation of CBF has precluded routine aggressive BP reduction.
Aim and Hypothesis: The primary study aim is to demonstrate the feasibility and safety of acute BP reduction to < 150 mmHg systolic using a standardized protocol in ICH patients. It is hypothesized that CTP will not demonstrate evidence of perihematoma ischemia following acute BP reduction.
Design: ICH ADAPT is a randomized blinded endpoint trial. Acutely hypertensive ICH patients are randomized to a target systolic BP of < 150 mmHg or < 180 mmHg. Patients are treated with intravenous (IV) labetalol/hydralazine/enalapril.
Study Outcomes: The primary outcome is cerebral blood flow in the perihematoma region, measured with CT perfusion, 2 hours after randomization. Secondary outcomes include the difference in BP at 1 and 2 hours post-randomization in the two treatment groups and hematoma expansion rates at 24 hours.
Discussion: ICH ADAPT is the only randomized trial designed specifically to identify any hemodynamic changes in the perihematoma region secondary to aggressive BP management. The results of this trial will facilitate ongoing and future studies aimed at determining the efficacy of rapid BP reduction in acute ICH.
- Labetalol HCl Drug
Intervention Desc: Labetalol HCl is an adrenergic receptor blocking agent that has both selective alpha1- and nonselective beta-adrenergic receptor blocking actions in a single substance.
- Hydralazine Hydrochloride (Apresoline)Drug
Intervention Desc: Apresoline, hydralazine hydrochloride USP, is an antihypertensive
- Enalaprilat (Vasotec; Renitec)Drug
Intervention Desc: Enalapril is an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension and some types of chronic heart failure.
- Labetalol/hydralazine/enalapril Drug
Intervention Desc: Blood pressure will be treated with intravenous labetalol (10 mg starting dose)/hydralazine (5 mg starting dose)/enalapril (1.25 mg starting dose). ARM 1: Kind: Experimental Label: Target systolic BP < 150 mmHg Description: Systolic blood pressure will be reduced to <150 mmHg within 1 hour of randomization. ARM 2: Kind: Experimental Label: Target systolic BP < 180 mmHg Description: Systolic blood pressure will be reduced, to <180 mmHg within 1 hour of randomization.
- Allocation: Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
ICH patients will be recruited from the Emergency Department of the University of Alberta. Informed consent, a screening questionnaire and blood work (including renal function indices) will be collected prior to enrollment. Baseline National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale scores and vital signs will be recorded, as will stroke risk factors, past medical history and medications, with particular emphasis on antihypertensives. Baseline complete blood count, coagulation profile and renal function tests will also be recorded. All patients will be randomized into either the treatment group or the control group. Those in the treatment group will receive a 10 mg intravenous bolus of labetalol, administered over 1 minute, along with a protocol designed to achieve and maintain systolic BP <150 mmHg within 1 hour of treatment. Patients randomized to the control group will be managed according to current American Stroke Association guidelines. One hour after initial treatment(two hours after randomization), all patients will undergo a standard non-contrast CT brain scan. Perfusion CT images will be acquired with the administration of intravenous iodinated contrast (40 ml) given over 10 seconds with CT images acquired every 0.5 seconds for 50 seconds. All patients will have a second non-contrast CT brain scan at 24 hours, in order to assess for additional hematoma expansion and peri-hematomal edema volume. Acute parenteral therapy will be administered only if systolic BP is ?180 mmHg. After 24 hours, the stroke team physician will manage BP in the manner they feel is appropriate. Physicians will be encouraged to start oral antihypertensive therapy, administered via nasogastric feeding tube if necessary, after the initial 24 hours.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Imaging marker (peri-hematomal rCBF, as measured with CT perfusion 2 hours after anti-hypertensive therapy is initiated).|
|Secondary||Hematoma expansion rates at 24 hours.|
|Primary||The primary outcome is cerebral blood flow in the perihematoma region, measured with CT perfusion, 2 hours after randomization.||2 hours post randomization||Yes|