Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial
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.


Options:
A: Inclusion Criteria:

* Aged 18 years or above
* Acute stroke due to spontaneous ICH confirmed by clinical history \& CT scan
* At least 2 systolic BP measurements of \>/=150mmHg and \</=220mmHg, recorded 2 or more minutes apart
* Able to commence randomly assigned BP lowering regimen within 6 hours of stroke onset
* Able to be actively treated and admitted to a monitored facility e.g. HDU/ICU/acute stroke unit

Exclusion Criteria:

* Known definite contraindication to an intensive BP lowering regimen
* Known definite indication for intensive BP lowering regimen as (or more) intensive than the active treatment arm
* Definite evidence that the ICH is secondary to a structural abnormality in the brain
* Previous ischaemic stroke within 30 days
* A very high likelihood that the patient will die within the next 24 hours on the basis of clinical and/or radiological criteria
* Known advanced dementia or significant pre-stroke disability
* Concomitant medical illness that would interfere with outcome assessments and follow up
* Already booked for surgical evacuation of haematoma
* Previous participation in this trial or current participation in another investigational drug trial
* A high likelihood that the patient will not adhere to the study treatment and follow up regimen
B: Inclusion Criteria:

* Clinical stroke syndrome with limb paresis, not likely to represent a transient ischaemic attack or non-stroke pathology (e.g. cerebral tumour)
* Systolic blood pressure ≥ 140 mm Hg
* Trial treatment possible within 30 hrs of symptom onset. If time of onset is not known, use the time when the patient was last known to be well.
* Consent (subsidiary, assent from legal acceptable representative, or waiver of consent)
* Age \>18 years

Exclusion Criteria:

* Markedly reduced consciousness (i.e. Scandinavian Stroke Scale consciousness score ≤ 2)
* Patient already receiving AT1 receptor blocker
* Contraindication to treatment with AT1 receptor blocker, e.g.:

  * known renal failure (women: creatinine ≥ 150 µmol/L; men: ≥ 180 µmol/L)
  * previously diagnosed bilateral renal artery stenosis
  * previously diagnosed high-grade aortic stenosis
  * previously diagnosed seriously impaired liver function and/or cholestasis
  * known intolerance to candesartan or other tablet ingredients
* Clear indication, in the clinician's view, for start of treatment with AT1 receptor blocker during the treatment period (e.g. chronic heart failure grade III-IV, in the presence of intolerance to ACE inhibitors)
* Clear indication, in the clinician's view, for antihypertensive therapy during the acute phase of stroke (i.e. concurrent hypertensive encephalopathy or aortic dissection, or other situations)
* Other serious or life-threatening disease before the stroke:
* Patient severely mentally or physically disabled (e.g. Mini Mental Status score \< 20, or modified Rankin Scale score ≥ 4)
* Life expectancy \< 12 months
* Patient unavailable for follow-up (e.g. no fixed address)
* Pregnant or breast-feeding woman
C: 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)
D: Inclusion Criteria:

* Adults ≥ 40 years old
* New unilateral arm weakness thought to be due to acute stroke within 3 hours of symptom onset
* Hypertension as defined by systolic BP \>160mm Hg on two consecutive seated or lying readings taken 5 - 10 minutes apart
* Conscious (eyes open spontaneously ie "A" on Alert, Voice, Pain, Unresponsive (AVPU) scale)
* Patient being transported to a PIL-FAST trial site (i.e. Royal Victoria Infirmary, North Tyneside General Hospital and Wansbeck General Hospital)
* Verbal consent obtained from participant or next of kin

Exclusion criteria:

* Age \< 40 years
* Females who are pregnant, lactating or at risk of pregnancy (i.e. who are not surgically sterile or at least 1 year post last menstrual period). Females \< 56 years of age consented by a relative will be excluded as menstrual history may be unknown.
* Any presentation of suspected stroke without unilateral arm weakness
* Cannot establish that stroke onset time (i.e. when patient was last seen well without symptoms) was within the last 3 hours
* Systolic BP \< 160mm Hg
* Reduced level of consciousness (below "A" on AVPU scale)
* Patient not being transported to PIL-FAST trial site
* Absence of participant or next of kin consent
* Known to be taking ACE-inhibitor or Angiotensin II Receptor Blocker medication already
* Known sensitivity to lisinopril or other ACE-inhibitor medication
* Pulse \> 120 beats per minute
* Seizure activity in this illness episode (witnessed or history)
* Hypoglycaemia (blood glucose \< 3.5 mmols/l)
* Cannot walk independently prior to stroke (walking stick / frame is allowed)
* Obvious understanding or memory problems when next of kin is absent
* Significant head trauma or brain surgery in the last 3 months
* Known renal failure
* Known liver failure (or currently jaundiced)
* Uncontrolled heart failure (breathlessness at rest)
* Receiving palliative care for known malignancy
* Currently enrolled in a clinical trial assessing a study drug

Answer: C