The purpose of this trial is to evaluate the safety and effectiveness of lowering blood pressure using nicardipine in persons with acute hypertension associated with intracerebral hemorrhage.
An estimated 37,000 to 52,400 people in the United States have intracerebral hemorrhage (ICH) every year. ICH——a form of stroke that has poor outcome and is difficult to treat——is associated with the highest mortality rate of all strokes. Hematoma expansion has been identified as the most common cause of neurological deterioration in persons with ICH. Early evidence suggests that acute hypertension (HTN)—or elevated blood pressure—may make some individuals more susceptible to hematoma expansion. Treating HTN acutely may prevent hematoma expansion, however, the effect of aggressive HTN treatment has not been determined.
The purpose of this trial is to evaluate the treatment feasibility and safety of lowering blood pressure using nicardipine——an antihypertensive medication——in persons who have acute HTN associated with ICH.
This pilot study will enroll 60 individuals who qualify with a presenting systolic blood pressure of at least 170 mmHg, have an ICH, and can be evaluated and treatment initiated within 6 hours of onset of stroke symptoms. In a stepwise fashion, the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 3 sequential levels: 170 to 200 mmHg, 140 to 170 mmHg, and 110 to 140 mmHg. Twenty participants will be enrolled per level.
Treatment will last 18 to 24 hours. Participants will stay in the hospital for about 7 days (including 24 hours in the intensive care unit for close monitoring) and will return for 1-hour follow-up visits at 30 days and at 90 days after discharge from the hospital. During these visits participants will receive neurological assessments to determine their functional outcome. For participants, the study will be completed after the 90-day follow-up visit.
- Nicardipine (Cardene)Drug
Other Names: Cardene, nicardipine hydrochloride Intervention Desc: Intravenous (IV) nicardipine infusion. It is expected that the treatment duration will vary between 18 and 24 hours. Started at 5mg/h Titrated by 2.5mg/hour every 15 minutes to bring systolic blood pressure in target range for the applicable Tier. Max dose 15mg/hour *Once target systolic blood pressure reached, dose decreased by 2.5mg/hour every 15 minutes until systolic blood pressure maintained in the target range or the medication is discontinued. ARM 1: Kind: Experimental Label: Tier 1 Description: Dose escalation the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg ARM 2: Kind: Experimental Label: Tier 2 Description: Dose escalation the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg ARM 3: Kind: Experimental Label: Tier 3 Description: Dose escalation the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
- Allocation: Non-Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety Study
- Intervention: Single Group Assignment
Step-wise, interventional design. Enrolled patients will be administered anti-hypertensive treatment to reduce systolic blood pressure to 170-200 mm Hg. Following success of this, patients will be graduated to the next two levels of blood pressure reduction (140-170 mm Hg and 110-140 mm Hg). Institutional DSMB approval will be required to move patients to the next level.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Tolerability, the ability to achieve reduction of blood pressure and maintain treatment goals (the specified systolic blood pressure range for the 18-24 hour period) without neurological deterioration or side effects.|
|Secondary||Safety, as determined by the amount of neurological deteriorations during the 24 hour treatment period, plus the number of serious adverse events|
|Primary||Tolerability, the ability to achieve reduction of blood pressure and maintain treatment goals (the specified systolic blood pressure range for the 18-24 hour period) without neurological deterioration or side effects||18-24 hour period||Yes|
|Primary||Feasibility, the Ability to Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.||Within 3 hours of symptom onset and sustained through 18-24 hours.||No|
|Primary||Safety, Acute, as Determined by the Amount of Neurological Deteriorations During the 24 Hour Treatment Period, Plus the Number of Serious Adverse Events.||within the first 72 hours of treatment initiation||Yes|
|Secondary||Tolerability, the Ability of Subjects to Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals||3 months||Yes|