Intervention: Nicardipine
Trial phase: Phase 3
ATC code: C08CA04
SMILES: COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)Cc2ccccc2)C1c1cccc([N+](=O)[O-])c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 500
Group description: Nicardipine hydrochloride was used according to need as the primary agent in lowering systolic blood pressure (SBP).

The goal for the standard blood pressure reduction group was to reduce and maintain SBP under 180 mmHg for 24 hours from randomization. The target SBP for this treatment arm was approximately 160 mmHg (the center of the assigned treatment group range of SBP 140-179 mmHg).

Nicardipine hydrochloride: IV nicardipine is initiated at a rate of 5 mg/hr, is continued, and is increased by 2.5 mg/hr increments every 15 min until the target SBP or maximum dose of 15 mg/hr is reached.

If SBP was greater than the target SBP despite infusion of the maximum nicardipine dose for 30 minutes, a second agent could be used (Labetalol 5-20 mg IV bolus every 15 min; urapidil substituted in countries without labetalol available) for another hour. Nicardipine use was to be decreased incrementally or was discontinued if SBP fell below the assigned treatment range.
Eligibility criteria:
Inclusion Criteria:

Age 18 years or older
IV nicardipine can be initiated within 4.5 hours of symptom onset.
Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
Total Glasgow Coma Scale (GCS) score (aggregate of verbal, eye, and motor response scores) of 5 or greater at time of emergency department (ED) arrival.
International normalized ratio (INR) value < 1.5
CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement <60 cc.
For subjects randomized prior to IV antihypertensive administration: SBP greater than 180 mmHg* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT spontaneous SBP reduction to below 180 mmHg at the time of randomization OR
For subjects randomized after IV antihypertensive administration: SBP greater than 180 mmHg* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT SBP reduction to below 140 mmHg at the time of randomization.

Informed consent obtained by subject, legally authorized representative, or next of kin.

Notes: The unit "mmHg" stands for "millimeters of mercury", a standard way of measuring blood pressure. Patients with SBP < 180 mmHg should be monitored for 4.5 hours from symptom onset as their SBP may rise to eligible levels before the eligibility window closes.

Exclusion Criteria:

ICH is due to previously known neoplasms, arteriovenous malformation (AVM), or aneurysms.
Intracerebral hematoma considered to be related to trauma.
ICH located in infratentorial regions such as pons or cerebellum.
Intraventricular hemorrhage (IVH) associated with intraparenchymal hemorrhage and blood completely fills one lateral ventricle or more than half of both ventricles.
Patient to receive immediate surgical evacuation.
Current pregnancy, or parturition within previous 30 days, or active lactation.
Use of dabigatran within the last 48 hours**.
A platelet count less than 50,000 per microliter (µL or mm3)
Known sensitivity to nicardipine.
Pre-morbid disability requiring assistance in ambulation or activities of daily living.
Subject's living will precludes aggressive ICU management.

Subject is currently participating in another interventional clinical trial

Use of dabigatran was clarified through investigator presentations, educational materials, and clinical tools to include newer similar class medications (such as rivaroxaban, apixaban, and edoxaban) that were being developed and in various stages of approval across enrolling countries through the course of this trial, in the event that patients using these medications may have been encountered during screening.