Antihypertensive Treatment in Acute Cerebral Hemorrhage
- Registration Number
- NCT00415610
- Lead Sponsor
- University of Minnesota
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- Age older than 18 years.
- Onset of new neurological signs of a stroke within 12 hours of the time to evaluation AND initiation of treatment with intravenous nicardipine.
- Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
- The total GCS score is greater than 8 at the time of enrollment.
- CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement less than 60 cc.
- ICH is supratentorial and is located in lobar, basal ganglionic, or thalamic based on the initial CT scan appearance.
- Admission systolic blood pressure greater than 170 mm Hg on two repeat measurements at least 5 minutes apart.
- Evidence of chronic hypertension.
- Subject is not considered a surgical candidate by the neurosurgery service.
- Time of symptom onset cannot be reliably assessed.
- Previously known neoplasms, arteriovenous malformation, or aneurysms.
- Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon.
- ICH is located in the cortex or infratentorial regions such as pons or cerebellum.
- Blood is visualized in the subarachnoid space.
- Intravenous nicardipine cannot be initiated within 12 hours of symptom onset.
- Use of clonidine hydrochloride and other central alpha-agonist within the last 48 hours that have the potential of withdrawal hypertension.
- Pregnancy, lactation, or parturition within previous 30 days.
- Any history of bleeding diathesis or coagulopathy, including the use of warfarin.
- Use of heparin in the previous 48 hours and a prolonged partial thromboplastin time.
- Known atrial-ventricular heart block other than first degree, or sick sinus syndrome without a pacemaker.
- Intolerance to calcium channel blockers.
- Exposure to study medication in the preceding 24 hours prior to enrollment.
- A platelet counts less than 100 000/mm3.
- Major surgery within the previous six weeks.
- History of any intracranial hemorrhage (including intracerebral or subarachnoid hemorrhage) or hemorrhagic stroke.
- Seizure at onset of stroke.
- Blood glucose less than 50 mg/dL or greater than 400 mg/dL.
- Current participation in another research drug treatment protocol.
- Isolated ventricular blood on CT scan.
- Subject has a living will that precludes aggressive intensive care unit management.
- Subject has acute myocardial infarction or renal failure that precludes use of aggressive antihypertensive therapy.
- Subjects with unstable angina or acute myocardial infarction within 2 weeks prior to ICH.
- Subjects with renal insufficiency with serum creatinine greater than 2.0 mg/dl or on renal dialysis.
- Sinus tachycardia exceeding 120 beats per minute or supraventricular tachycardia is observed during initial evaluation.
- Ischemic stroke within 4 weeks of presentation.
- Congestive heart failure graded as class III and IV by New York Heart Association (NYHA) classification.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tier 1 nicardipine Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 170 to 200 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician. Tier 2 nicardipine Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 140 to 170 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician. Tier 3 nicardipine Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 110 to 140 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.
- Primary Outcome Measures
Name Time Method Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier. Within 3 hours of symptom onset and sustained through 18-24 hours. Feasibility of treatment was assessed by whether SBP reduction and maintenance within the respective target range was achieved (treatment success) or not (treatment failure), and secondarily by whether a significant difference between treatment arms was achieved. Treatment failure was defined based on the observed hourly hourly minimum SBP remaining greater than the upper limit of the target range for 2 consecutive hours after initiation of nicardipine infusion. Spontaneous decline of SBP below the lower limit of the specific tier was not considered treatment failure as all such declines were asymptomatic.The lower number in the more intensive treatment groups reflects in part the greater challenge of rapidly lowering systolic blood pressure to a more intensive (lower) range, as a higher number of treatment failures as pre-defined by meeting the SBP range goal within 3 hours of symptom onset in this group predictably occurred.
Total Number of Serious Adverse Events Within the Initial 72 Hours From Treatment Per Subject from treatment initiation through 72 hours Serious adverse events were ascertained by site investigators using FDA-defined guidelines, defined as any untoward clinical events having been fatal, life-threatening, resulting in new or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage. Subjects were followed closely from randomization through 90 days. The initial 72-hour period was chosen as the most meaningful time period for which to examine SAEs likely to be related to the acute safety of the study treatment.
Number of Participants With Neurological Deteriorations (Decrease of 2 or More Points on the GCS Score or an Increase of 4 or More Points on the NIHSS Score) During the 24 Hour Treatment", within the first 72 hours of treatment initiation Neurological status was monitored quantitatively and independently of other adverse events using two scales. The Glasgow Coma Scale (GCS) score measures level of consciousness in eye, motor, and verbal components. At least one point is given in each category. The scale ranges from 3 to 15, with 3 indicating deep unconsciousness and 15 indicating consciousness is not impaired. The National Institutes of Health Stroke Scale (NIHSS) quantifies neurologic deficits in 11 categories. Level of consciousness, horizontal eye movements, visual fields, facial palsy, movement in each limb, sensation, language and speech, and extinction or inattention on one side of the body are tested. Scores range from 0 to 42; 0 indicates normal function and higher scores indicate greater deficit severity.
- Secondary Outcome Measures
Name Time Method Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals 3 months The ability to maintain the Specified Systolic Blood Pressure Range for the 18-24 Hour Period without Neurological Deterioration or Side Effects
Trial Locations
- Locations (12)
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Clinical Coordinating Center: University of Minnesota, Fairview Hospital
🇺🇸Minneapolis, Minnesota, United States
Kansas University Medical Center
🇺🇸Kansas City, Kansas, United States
Massachusetts General/Brigham Women's Hospital
🇺🇸Boston, Massachusetts, United States
The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center
🇺🇸Kansas City, Kansas, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
University of Medicine and Dentistry of New Jersey
🇺🇸Newark, New Jersey, United States
University of Southern California
🇺🇸Los Angeles, California, United States
JFK Medical Center
🇺🇸Edison, New Jersey, United States
Statistical Coordinating Center: Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States