Trial Outcomes & Findings for Antihypertensive Treatment in Acute Cerebral Hemorrhage (NCT NCT00415610)
NCT ID: NCT00415610
Last Updated: 2017-11-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
60 participants
Primary outcome timeframe
Within 3 hours of symptom onset and sustained through 18-24 hours.
Results posted on
2017-11-21
Participant Flow
Patients 18 years and older presenting to site hospital ED and ICU areas within 6 hours of symptom onset for ≤ 60 cc volume intracerebral hemorrhage, with GCS ≥ 8, systolic blood pressure ≥ 170 mmHg and meeting all inclusion/exclusion criteria were enrolled following consent by themselves or a family member/legally authorized representative.
A progressive, three-tiered approach to lowering systolic blood pressure with DSMB review after enrollment in each successive SBP range was completed. Safety was determined at each level before progressing to the next. Subjects meeting criteria and consenting to participate were considered enrolled and have been included in the data analysis.
Participant milestones
| Measure |
Tier 1
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
18
|
20
|
22
|
|
Overall Study
COMPLETED
|
15
|
18
|
17
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
5
|
Reasons for withdrawal
| Measure |
Tier 1
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Overall Study
Death
|
3
|
2
|
5
|
Baseline Characteristics
Antihypertensive Treatment in Acute Cerebral Hemorrhage
Baseline characteristics by cohort
| Measure |
Tier 1
n=18 Participants
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.
nicardipine: 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.
|
Tier 2
n=20 Participants
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.
nicardipine: 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.
|
Tier 3
n=22 Participants
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.
nicardipine: 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.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
62 years
STANDARD_DEVIATION 17.7 • n=5 Participants
|
58.5 years
STANDARD_DEVIATION 13.0 • n=7 Participants
|
65.1 years
STANDARD_DEVIATION 14.6 • n=5 Participants
|
62 years
STANDARD_DEVIATION 15.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
5 participants
n=5 Participants
|
13 participants
n=7 Participants
|
13 participants
n=5 Participants
|
31 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black
|
11 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
25 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Others
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
20 participants
n=7 Participants
|
22 participants
n=5 Participants
|
60 participants
n=4 Participants
|
|
Baseline Measures - Timing of Treatment
Symptom onset to emergency department arrival
|
1.72 hours
STANDARD_DEVIATION 1.27 • n=5 Participants
|
1.70 hours
STANDARD_DEVIATION 1.13 • n=7 Participants
|
1.86 hours
STANDARD_DEVIATION 1.78 • n=5 Participants
|
1.72 hours
STANDARD_DEVIATION 1.37 • n=4 Participants
|
|
Baseline Measures - Timing of Treatment
Symptom onset to treatment initiation
|
3.94 hours
STANDARD_DEVIATION 1.45 • n=5 Participants
|
4.13 hours
STANDARD_DEVIATION 1.50 • n=7 Participants
|
4.44 hours
STANDARD_DEVIATION 2.08 • n=5 Participants
|
4.19 hours
STANDARD_DEVIATION 1.71 • n=4 Participants
|
|
Initial SBP
|
209 millimeters of mercury (mmHg)
n=5 Participants
|
212 millimeters of mercury (mmHg)
n=7 Participants
|
201 millimeters of mercury (mmHg)
n=5 Participants
|
208 millimeters of mercury (mmHg)
n=4 Participants
|
|
Initial Hematoma Volume
|
15.45 cubic centimeters
STANDARD_DEVIATION 14.60 • n=5 Participants
|
14.84 cubic centimeters
STANDARD_DEVIATION 17.15 • n=7 Participants
|
10.94 cubic centimeters
STANDARD_DEVIATION 10.87 • n=5 Participants
|
13.56 cubic centimeters
STANDARD_DEVIATION 14.24 • n=4 Participants
|
|
Baseline Measures of stroke symptom severity
Initial NIHSS score
|
11 units on a scale
n=5 Participants
|
9 units on a scale
n=7 Participants
|
8 units on a scale
n=5 Participants
|
10 units on a scale
n=4 Participants
|
|
Baseline Measures of stroke symptom severity
Initial GCS
|
14 units on a scale
n=5 Participants
|
15 units on a scale
n=7 Participants
|
15 units on a scale
n=5 Participants
|
15 units on a scale
n=4 Participants
|
|
Duration of nicardipine infusion
|
12.93 hours
STANDARD_DEVIATION 13.5 • n=5 Participants
|
30.06 hours
STANDARD_DEVIATION 23.8 • n=7 Participants
|
45.82 hours
STANDARD_DEVIATION 37.3 • n=5 Participants
|
31.69 hours
STANDARD_DEVIATION 30.75 • n=4 Participants
|
|
Maximum Dose of Nicardipine Used
|
8.47 milligrams
STANDARD_DEVIATION 5.75 • n=5 Participants
|
8.90 milligrams
STANDARD_DEVIATION 4.48 • n=7 Participants
|
12.52 milligrams
STANDARD_DEVIATION 6.76 • n=5 Participants
|
10.10 milligrams
STANDARD_DEVIATION 5.98 • n=4 Participants
|
PRIMARY outcome
Timeframe: Within 3 hours of symptom onset and sustained through 18-24 hours.Population: All subjects were evaluated for achievement of the treatment goals.
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.
Outcome measures
| Measure |
Tier 1
n=18 Participants
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
n=20 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
n=22 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.
Meeting Criteria of initial SBP > 170 mmHg
|
18 participants
|
20 participants
|
22 participants
|
|
Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.
Number treated within 3 hours of symptom onset
|
7 participants
|
5 participants
|
6 participants
|
|
Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.
Treatment Failure, SBP not in range by 2 hours
|
0 participants
|
0 participants
|
9 participants
|
PRIMARY outcome
Timeframe: within the first 72 hours of treatment initiationPopulation: All subjects entered in the trial were followed and their data analyzed for safety measures. Not all subjects entered in the trial survived or remained in the trial to assess final outcomes at 1 or 3 months. When safety stopping rules could not have triggered after 18 initial subjects recruitment was adjusted to weight the subsequent tiers.
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.
Outcome measures
| Measure |
Tier 1
n=18 Participants
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
n=20 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
n=22 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
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",
|
1 participants
|
2 participants
|
4 participants
|
PRIMARY outcome
Timeframe: from treatment initiation through 72 hoursPopulation: All subjects entered in the trial were followed and their data analyzed for safety measures. Not all subjects entered in the trial survived or remained in the trial to assess final outcomes at 1 or 3 months. When safety stopping rules could not have triggered after 18 initial subjects recruitment was adjusted to weight the subsequent tiers.
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.
Outcome measures
| Measure |
Tier 1
n=18 Participants
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
n=20 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
n=22 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Total Number of Serious Adverse Events Within the Initial 72 Hours From Treatment Per Subject
|
0 Participants
|
1 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: All subjects were analyzed by treatment arm for the presence of SAEs, neurological deterioration, symptomatic or asymptomatic hematoma expansion, and mortality in-hospital or within 3 months. Pre-specified safety stopping rules were used. The nature and relatedness of events was examined and overseen by an external Data safety and Monitoring Board.
The ability to maintain the Specified Systolic Blood Pressure Range for the 18-24 Hour Period without Neurological Deterioration or Side Effects
Outcome measures
| Measure |
Tier 1
n=18 Participants
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
n=20 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
n=22 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with SAE within 72 hours
|
0 participants
|
1 participants
|
3 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with neurologic deterioration within 24 hours
|
1 participants
|
2 participants
|
4 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with symptomatic hematoma expansion
|
0 participants
|
1 participants
|
4 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with asymptomatic hematoma expansion
|
6 participants
|
2 participants
|
3 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with in-hospital mortality
|
2 participants
|
1 participants
|
1 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with 3-month mortality
|
3 participants
|
2 participants
|
5 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with 1-month favorable outcome, mRS 0-2
|
4 participants
|
6 participants
|
4 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N missing for 1-month outcome assessment
|
3 participants
|
3 participants
|
2 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N with 3-month favorable outcome, mRS 0-2
|
8 participants
|
9 participants
|
7 participants
|
|
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
N missing for 3-month outcome assessment
|
3 participants
|
4 participants
|
2 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From enrollment through 3 monthsPopulation: Serious adverse events were monitored for all patients throughout the 3-month study period; when mortality resulted death was categorized as having occurred prior to or following hospital discharge. The 3-month mortality count includes deaths that occurred earlier. Survival was confirmed at hospital discharge, 1 month, and 3 months.
The tolerability of the study treatment was further ascertained by examination of in-hospital, 1-month, or 3-month mortality in each treatment group. This pilot study was not powered (did not plan to enroll an adequate number of patients) to draw meaningful conclusions about individual adverse event categories, outcome measures, or to make comparisons between the treatment arms beyond the overall feasibility and tolerability of rapidly and significantly lowering SBP following intracerebral hemorrhage. The timing and magnitude of SBP reduction was also compared to the timing of individual safety events to further evaluate possible relationships between the study treatment, adverse events, and any recognizable safety concerns. This information is available in publication but is not able to be displayed on this website due to formatting restrictions.
Outcome measures
| Measure |
Tier 1
n=18 Participants
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
n=20 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
n=22 Participants
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Particpants Who 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 Resulting in Death.
In-hospital mortality
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Particpants Who 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 Resulting in Death.
Mortality at 3 months (also in participant flow)
|
3 Participants
|
2 Participants
|
5 Participants
|
|
Particpants Who 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 Resulting in Death.
Survival/no known death at 1 or 3 months (derived)
|
13 Participants
|
17 Participants
|
16 Participants
|
Adverse Events
Tier 1
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Tier 2
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Tier 3
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tier 1
n=18 participants at risk
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
n=20 participants at risk
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
n=22 participants at risk
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/18 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
5.0%
1/20 • Number of events 1 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
0.00%
0/22 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/18 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
0.00%
0/20 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
4.5%
1/22 • Number of events 1 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome (ARDS)
|
0.00%
0/18 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
0.00%
0/20 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
4.5%
1/22 • Number of events 1 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
|
Metabolism and nutrition disorders
Hyperglycemia and hypokalemia
|
0.00%
0/18 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
0.00%
0/20 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
4.5%
1/22 • Number of events 1 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
|
Nervous system disorders
Symptomatic hematoma volume expansion
|
0.00%
0/18 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
5.0%
1/20 • Number of events 1 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
0.00%
0/22 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
Other adverse events
| Measure |
Tier 1
n=18 participants at risk
Dose escalation: Initial range
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 170 to 200 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 2
n=20 participants at risk
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg
Nicardipine: 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.
The DSMB will review safety, tolerability, and feasibility before escalation to the next level.
|
Tier 3
n=22 participants at risk
Dose escalation:
The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg
Nicardipine: 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.
|
|---|---|---|---|
|
Nervous system disorders
Neurological deterioration within 24 hours
|
5.6%
1/18 • Number of events 1 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
10.0%
2/20 • Number of events 2 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
18.2%
4/22 • Number of events 4 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
|
Nervous system disorders
Asymptomatic hematoma expansion
|
33.3%
6/18 • Number of events 6 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
10.0%
2/20 • Number of events 2 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
13.6%
3/22 • Number of events 3 • SAEs were collected from randomization through 90 +/- 14 days, but are reported through 72 hours (meaningful time in relation to treatment). Other AEs were collected through seven days from randomization or until hospital discharge, whichever came first.
Safety stopping rules were established in the protocol based on the upper limit (by 95% confidence interval) for individual and cumulative rates of neurologic deterioration and serious adverse events (SAE) from previous studies in a manner similar to other phase I trials in acute stroke patents. Safety data was monitored by the NIH-appointed DSMB.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place