Clinical trial NCT00963976: Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial
Official title: Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intracerebral Hemorrhage
Keywords: Stroke
Hypertension
Cerebral Blood Flow
CT Perfusion
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Canada
name: Alberta Heritage Foundation for Medical Research
First posted: 2009-08-24
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* Acute primary ICH demonstrated with CT scan
* Onset ≤ 24 h prior to randomization

Exclusion Criteria:

* Contraindication to BP reduction i.e., severe arterial stenosis or high-grade stenotic valvular heart disease
* Indication for urgent BP reduction i.e., hypertensive encephalopathy, or aortic dissection
* Definite evidence that the ICH is secondary to underlying cerebral or vascular pathology, i.e., AVM, aneurysm, tumour, trauma, vasculitis, or hemorrhagic transformation of an ischemic infarct
* Previous ischemic stroke within 30 days of current event NB: Prior ICH is not an exclusion criterion
* Planned surgical resection of hematoma NB: Extraventricular Drain placement is not an exclusion criterion
* Contraindication to CT perfusion imaging (i.e. contrast allergy, metformin use or Creatinine \>160 μmol/l)

Primary outcomes:
measure: The primary outcome is cerebral blood flow in the perihematoma region, measured with CT perfusion, 2 hours after randomization.
timeFrame: 2 hours post randomization
Secondary outcomes:
measure: Hematoma expansion rates at 24 hours.
timeFrame: 24 hours post randomization
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nuns Hospital
state: Alberta
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
Study officials:
References:
citation: Klahr AC, Kosior JC, Dowlatshahi D, Buck BH, Beaulieu C, Gioia LC, Kalashyan H, Wilman AH, Jeerakathil T, Emery DJ, Shuaib A, Butcher KS. Lower Blood Pressure Is Not Associated With Decreased Arterial Spin Labeling Estimates of Perfusion in Intracerebral Hemorrhage. J Am Heart Assoc. 2019 Jun 4;8(11):e010904. doi: 10.1161/JAHA.118.010904.
citation: McCourt R, Gould B, Kate M, Asdaghi N, Kosior JC, Coutts S, Hill MD, Demchuk A, Jeerakathil T, Emery D, Butcher KS. Blood-brain barrier compromise does not predict perihematoma edema growth in intracerebral hemorrhage. Stroke. 2015 Apr;46(4):954-60. doi: 10.1161/STROKEAHA.114.007544. Epub 2015 Feb 19.
citation: Gould B, McCourt R, Gioia LC, Kate M, Hill MD, Asdaghi N, Dowlatshahi D, Jeerakathil T, Coutts SB, Demchuk AM, Emery D, Shuaib A, Butcher K; ICH ADAPT Investigators. Acute blood pressure reduction in patients with intracerebral hemorrhage does not result in borderzone region hypoperfusion. Stroke. 2014 Oct;45(10):2894-9. doi: 10.1161/STROKEAHA.114.005614. Epub 2014 Aug 21.
citation: McCourt R, Gould B, Gioia L, Kate M, Coutts SB, Dowlatshahi D, Asdaghi N, Jeerakathil T, Hill MD, Demchuk AM, Buck B, Emery D, Butcher K; ICH ADAPT Investigators. Cerebral perfusion and blood pressure do not affect perihematoma edema growth in acute intracerebral hemorrhage. Stroke. 2014 May;45(5):1292-8. doi: 10.1161/STROKEAHA.113.003194. Epub 2014 Apr 1.
citation: Butcher KS, Jeerakathil T, Hill M, Demchuk AM, Dowlatshahi D, Coutts SB, Gould B, McCourt R, Asdaghi N, Findlay JM, Emery D, Shuaib A; ICH ADAPT Investigators. The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial. Stroke. 2013 Mar;44(3):620-6. doi: 10.1161/STROKEAHA.111.000188. Epub 2013 Feb 7.
citation: Butcher K, Jeerakathil T, Emery D, Dowlatshahi D, Hill MD, Sharma M, Buck B, Findlay M, Lee TY, Demchuk AM. The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial: ICH ADAPT. Int J Stroke. 2010 Jun;5(3):227-33. doi: 10.1111/j.1747-4949.2010.00431.x.