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Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)

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ClinicalTrials.gov Identifier: NCT00415610
Recruitment Status : Completed
First Posted : December 25, 2006
Results First Posted : September 7, 2015
Last Update Posted : November 21, 2017
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Intracerebral Hemorrhage
Hypertension
Stroke
Intervention Drug: nicardipine
Enrollment 60
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Tier 1 Tier 2 Tier 3
Hide Arm/Group Description

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.

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.

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.
Period Title: Overall Study
Started 18 20 22
Completed 15 18 17
Not Completed 3 2 5
Reason Not Completed
Death             3             2             5
Arm/Group Title Tier 1 Tier 2 Tier 3 Total
Hide Arm/Group Description

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.

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.

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 of all reporting groups
Overall Number of Baseline Participants 18 20 22 60
Hide Baseline Analysis Population Description
Group numbers were adjusted as adequate safety parameters were met in each successive treatment tier. A larger number of subjects were therefore evaluated in the final tier where safety is of greatest concern and SBP parameter is also of greatest challenge to meet.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 20 participants 22 participants 60 participants
62  (17.7) 58.5  (13.0) 65.1  (14.6) 62  (15.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 20 participants 22 participants 60 participants
Female
9
  50.0%
8
  40.0%
9
  40.9%
26
  43.3%
Male
9
  50.0%
12
  60.0%
13
  59.1%
34
  56.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 20 participants 22 participants 60 participants
White 5 13 13 31
Black 11 7 7 25
Others 2 0 2 4
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants 20 participants 22 participants 60 participants
18 20 22 60
Baseline Measures - Timing of Treatment   [1] 
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 18 participants 20 participants 22 participants 60 participants
Symptom onset to emergency department arrival 1.72  (1.27) 1.70  (1.13) 1.86  (1.78) 1.72  (1.37)
Symptom onset to treatment initiation 3.94  (1.45) 4.13  (1.50) 4.44  (2.08) 4.19  (1.71)
[1]
Measure Description: as mean time in hours from symptom onset
Initial SBP   [1] 
Median (Full Range)
Unit of measure:  Millimeters of mercury (mmHg)
Number Analyzed 18 participants 20 participants 22 participants 60 participants
209
(178 to 255)
212
(190 to 275)
201
(171 to 300)
208
(171 to 300)
[1]
Measure Description: as measured on ED arrival by automated cuff inflation device
Initial Hematoma Volume   [1] 
Mean (Standard Deviation)
Unit of measure:  Cubic centimeters
Number Analyzed 18 participants 20 participants 22 participants 60 participants
15.45  (14.60) 14.84  (17.15) 10.94  (10.87) 13.56  (14.24)
[1]
Measure Description: as measured by central reader (vs. rapid ABC/2 method used for initial qualification), in cubic centimeters estimated total volume
Baseline Measures of stroke symptom severity   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 18 participants 20 participants 22 participants 60 participants
Initial NIHSS score
11
(2 to 40)
9
(0 to 25)
8
(3 to 34)
10
(0 to 40)
Initial GCS
14
(9 to 15)
15
(8 to 15)
15
(9 to 15)
15
(8 to 15)
[1]
Measure Description: As measured on ED arrival. The Glasgow Coma Scale (GCS) is most applicable in those critically ill and measures eye opening, verbal, and motor responses. Scores on the 3-component GCS may range from 3-15 and a lower score indicates a more severe condition. The National Institutes of Health Stroke Scale (NIHSS) is more sensitive for discerning subtle symptoms. Scores on the 11-component NIHSS may total between 0-42, with a higher score indicating a more severe stroke. ICH is an evolving condition and may worsen. NIHSS and GCS scores are used to measure changes in neurological status over time.
Duration of nicardipine infusion   [1] 
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 18 participants 20 participants 22 participants 60 participants
12.93  (13.5) 30.06  (23.8) 45.82  (37.3) 31.69  (30.75)
[1]
Measure Description: in total hours, as measured from initial start to final stop of any nicardipine administration
Maximum Dose of Nicardipine Used   [1] 
Mean (Standard Deviation)
Unit of measure:  Milligrams
Number Analyzed 18 participants 20 participants 22 participants 60 participants
8.47  (5.75) 8.90  (4.48) 12.52  (6.76) 10.10  (5.98)
[1]
Measure Description: in total milligrams, as calculated by rate per hour by nicardipine volume % for total hours of infusion
1.Primary Outcome
Title Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.
Hide Description 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.
Time Frame Within 3 hours of symptom onset and sustained through 18-24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects were evaluated for achievement of the treatment goals.
Arm/Group Title Tier 1 Tier 2 Tier 3
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 18 20 22
Measure Type: Number
Unit of Measure: participants
Meeting Criteria of initial SBP > 170 mmHg 18 20 22
Number treated within 3 hours of symptom onset 7 5 6
Treatment Failure, SBP not in range by 2 hours 0 0 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tier 1, Tier 2, Tier 3
Comments The hourly average (of maximum and minimum) SBP measurements were graphed with box-and-whiskers plot. In addition, a repeated measures analysis of the 25 average SBP (baseline and subsequent 24 hourly measures) was conducted with a mixed effects model (assuming autoregressive covariance structure in SAS version 9.1 PROC MIXED) to determine statistically the effect of treatment intensity (tier) on the average SBP over the 24 hrs with and without adjustment for baseline NIHSS score and age.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.01
Comments The repeated measure analysis of the hourly average SBP was calculated with and without adjusting for baseline NIHSS and age.
Method repeated measure
Comments Adjusted for initial deficit severity of using baseline NIHSS instead of GCS to better discriminate among patients with GCS score > 8.
2.Primary Outcome
Title 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",
Hide Description 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.
Time Frame within the first 72 hours of treatment initiation
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tier 1 Tier 2 Tier 3
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 18 20 22
Measure Type: Number
Unit of Measure: participants
1 2 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tier 1, Tier 2, Tier 3
Comments Done as a surrogate to evaluate the relationship between early SBP reduction and safety events.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .5
Comments Observed average SBP change at 2 hrs after treatment initiation between subjects who did or did not have neurologic deterioration within 24 hrs.
Method Wilcoxon rank sum test
Comments Mean decrease measured for subjects with neurological deterioration and subjects without neurological deterioration.
3.Primary Outcome
Title Total Number of Serious Adverse Events Within the Initial 72 Hours From Treatment Per Subject
Hide Description 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.
Time Frame from treatment initiation through 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tier 1 Tier 2 Tier 3
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 18 20 22
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   5.0%
3
  13.6%
4.Secondary Outcome
Title Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
Hide Description The ability to maintain the Specified Systolic Blood Pressure Range for the 18-24 Hour Period without Neurological Deterioration or Side Effects
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tier 1 Tier 2 Tier 3
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 18 20 22
Measure Type: Number
Unit of Measure: participants
N with SAE within 72 hours 0 1 3
N with neurologic deterioration within 24 hours 1 2 4
N with symptomatic hematoma expansion 0 1 4
N with asymptomatic hematoma expansion 6 2 3
N with in-hospital mortality 2 1 1
N with 3-month mortality 3 2 5
N with 1-month favorable outcome, mRS 0-2 4 6 4
N missing for 1-month outcome assessment 3 3 2
N with 3-month favorable outcome, mRS 0-2 8 9 7
N missing for 3-month outcome assessment 3 4 2
5.Other Pre-specified Outcome
Title 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.
Hide Description

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.

Time Frame From enrollment through 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tier 1 Tier 2 Tier 3
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 18 20 22
Measure Type: Count of Participants
Unit of Measure: Participants
In-hospital mortality
2
  11.1%
1
   5.0%
1
   4.5%
Mortality at 3 months (also in participant flow)
3
  16.7%
2
  10.0%
5
  22.7%
Survival/no known death at 1 or 3 months (derived)
13
  72.2%
17
  85.0%
16
  72.7%
Time Frame 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Tier 1 Tier 2 Tier 3
Hide Arm/Group Description

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.

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.

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.
All-Cause Mortality
Tier 1 Tier 2 Tier 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Tier 1 Tier 2 Tier 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      1/20 (5.00%)      3/22 (13.64%)    
Metabolism and nutrition disorders       
Hyperglycemia and hypokalemia  1  0/18 (0.00%)  0 0/20 (0.00%)  0 1/22 (4.55%)  1
Nervous system disorders       
Symptomatic hematoma volume expansion  1 [1]  0/18 (0.00%)  0 1/20 (5.00%)  1 0/22 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Respiratory distress  1  0/18 (0.00%)  0 1/20 (5.00%)  1 0/22 (0.00%)  0
Acute respiratory failure  1  0/18 (0.00%)  0 0/20 (0.00%)  0 1/22 (4.55%)  1
Acute respiratory distress syndrome (ARDS)  1  0/18 (0.00%)  0 0/20 (0.00%)  0 1/22 (4.55%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (4.1)
[1]
defined as > 33 % increase in hematoma volume as measured by central reader between baseline and 24 hour head CT scans, accompanied by neurological deterioration or new neurological symptoms
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tier 1 Tier 2 Tier 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/18 (38.89%)      4/20 (20.00%)      7/22 (31.82%)    
Nervous system disorders       
Neurological deterioration within 24 hours  1 [1]  1/18 (5.56%)  1 2/20 (10.00%)  2 4/22 (18.18%)  4
Asymptomatic hematoma expansion  1 [2]  6/18 (33.33%)  6 2/20 (10.00%)  2 3/22 (13.64%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (4.1)
[1]
defined as increase of 4 or more points on NIHSS or decrease of 2 or more points on GCS
[2]
Hematoma expansion is defined as > 33% increase in hematoma volume as measured by central reader between baseline and 24 hour head CT scans
Limited by small sample size and likelihood of imbalances in subject characteristics among the three tiers. Clinical measures may be insensitive. Not designed to provide comparative event rates and not powered toward prediction of clinical outcomes.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Adnan I Qureshi, MD
Organization: University of Minnesota
Phone: 612-624-2431
EMail: qureshai@gmail.com
Publications of Results:
Layout table for additonal information
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00415610     History of Changes
Other Study ID Numbers: 0609M93128
R01NS044976-01A2 ( U.S. NIH Grant/Contract )
First Submitted: December 21, 2006
First Posted: December 25, 2006
Results First Submitted: March 3, 2015
Results First Posted: September 7, 2015
Last Update Posted: November 21, 2017