Brain Ischemia
Conditions
Keywords
Blood Pressure, Atherosclerosis, Brain Ischemia
Brief summary
To develop adequate blood pressure (BP) lowering strategy after subacute ischemic stroke patients with symptomatic severe intracranial atherosclerosis. Primary hypothesis of this study is that aggressive BP control (lowering systolic BP between 110mmHg and 120mmHg) will not increase the ischemic lesion volumes in hemisphere compared to modest BP lowering (lowering systolic BP between 130mmHg and 140mmHg) in the patients with symptomatic severe intracranial atherosclerosis.
Detailed description
The benefits of BP lowering in the prevention of primary and secondary prevention of stroke is established well, although absolute target BP level is uncertain. Current guidelines defined the normal BP as \<120/80mmHg and recommend individualized target BP level. Large well performed stroke prevention trials consistently showed that reduction of 10/5mmHg in patients with systolic BP below 140mmHg had clear benefits in the prevention of cardiovascular events. However, we have a dilemma about BP control in the patients with severe intracranial atherosclerosis. Aggressive BP control will be more effective in the prevention of overall cardiovascular events than modest BP control, but aggressive BP control will reduce cerebral perfusion in the territory of severe intracranial disease and may increase the risk of ischemic damage. The study will try to reveal aggressive BP control in the patients with symptomatic severe intracranial atherosclerosis is not increase ischemic lesion volume in hemisphere to compare modest BP control.
Interventions
PROCEDUREAggressive BP lowering
adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level
PROCEDUREmodest blood pressure lowering
adjust the amount and number of antihypertensive drugs
Sponsors
Pfizer
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* acute symptomatic ischemic stroke having relevant lesion on DWI(Diffusion weighted image) MRI 7 days after and 42 days within onset. * relevant stenosis(more than 50%) or occlusion from MCA(middle cerebral artery)(M1) to distal of ICA(internal carotid artery ) on MR(Magnetic resonance) angiogram or CT angiogram. * mean systolic blood pressure\>=140mmHg or taking antihypertensive drug on screening.
Exclusion criteria
* taking more than 3 antihypertensive drugs and mean systolic blood pressure\>=150mmHg on screening. * history of recent thrombolysis but stenosis or occlusion remained after thrombolysis. * evidence of orthostatic hypotension * suspicious embolic cerebrovascular stenosis * planned state of cerebrovascular surgery or angioplasty or stent 7 months within screening. * severe stroke-NIHSS\>=16 * mean systolic blood pressure\>=200mmHg which is not able to control on screening. * abnormal blood test finding (abnormal LFT(liver function test), anemia, renal insufficiency) * pregnant or breast-feeding * severe stroke sequela or medical problem * suspicious secondary hypertension * disease causing edema or significant ankle edema on screening. * severe heart failure which correspond to NYHA (New York Heart Association )heart failure classification class III or IV. * inappropriate condition determined by investigator * Patient who do not have FLAIR image on or two months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | Screening to 24 weeks | The difference between final ischemic lesions volume and base ischemic lesions of both hemisphere on FLAIR MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI | 24 weeks | — |
| Number of Participants With Cardiovascular Events From Screening to Week 24 in ITT Population. | 24 weeks | — |
| Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | 24 weeks | the difference between final ischemic lesions volume and base ischemic lesions in the territory of symptomatic intracranial disease on FLAIR MRI |
| Number of Participants With Vascular Death From Screening to Week 24 in ITT Population. | 24 Weeks | — |
| Number of Participants With Adverse Events | 24 Weeks | Number of Participants with Adverse Events |
| Total Number of Cardiovascular Events Form Screening to Week 24 in ITT Population. | 24 Week | — |
Countries
South Korea
Participant flow
Recruitment details
The recruitment period of this study was from 07/Apr/2010 to 2/Apr/2014 and there had been recruited at medical clinic.
Pre-assignment details
There were not any significant events and approaches for the overall study following participant enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Aggressive BP Lowering Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level | 66 |
| Modest BP Lowering Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs | 63 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | low compliance | 1 | 1 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Aggressive BP Lowering | Modest BP Lowering | Total |
|---|---|---|---|
| Age, Customized | 64.8 years STANDARD_DEVIATION 8.5 | 63.5 years STANDARD_DEVIATION 11.2 | 64.2 years STANDARD_DEVIATION 9.85 |
| Gender Female | 25 Participants | 27 Participants | 52 Participants |
| Gender Male | 41 Participants | 36 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / 65 | 47 / 65 |
| serious Total, serious adverse events | 10 / 65 | 8 / 65 |
Outcome results
Primary
Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI)
The difference between final ischemic lesions volume and base ischemic lesions of both hemisphere on FLAIR MRI
Time frame: Screening to 24 weeks
Population: The Number of Participants Analyzed by FAS(Full analysis)Population. FAS Population (Aggressive BP Lowering: 59, Modest BP Lowering: 52)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aggressive BP Lowering | Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | Screening | 11.2 cc | Standard Deviation 24.1 |
| Aggressive BP Lowering | Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | Week 24 | 16.1 cc | Standard Deviation 39.3 |
| Aggressive BP Lowering | Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | Change from Screening to Week 24 | 4.9 cc | Standard Deviation 18.3 |
| Modest BP Lowering | Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | Screening | 10.4 cc | Standard Deviation 19.4 |
| Modest BP Lowering | Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | Week 24 | 12.6 cc | Standard Deviation 20 |
| Modest BP Lowering | Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | Change from Screening to Week 24 | 2.2 cc | Standard Deviation 8.2 |
Secondary
Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population
the difference between final ischemic lesions volume and base ischemic lesions in the territory of symptomatic intracranial disease on FLAIR MRI
Time frame: 24 weeks
Population: The number of participants are analyzed by FAS population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aggressive BP Lowering | Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | Screening | 10.2 cc | Standard Deviation 22.6 |
| Aggressive BP Lowering | Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | Week 24 | 15.0 cc | Standard Deviation 38.6 |
| Aggressive BP Lowering | Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | Change from Screening to Week 24 | 4.9 cc | Standard Deviation 18.3 |
| Modest BP Lowering | Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | Screening | 9.9 cc | Standard Deviation 19.4 |
| Modest BP Lowering | Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | Week 24 | 12.0 cc | Standard Deviation 20 |
| Modest BP Lowering | Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | Change from Screening to Week 24 | 2.1 cc | Standard Deviation 8.2 |
Secondary
Number of Participants With Adverse Events
Number of Participants with Adverse Events
Time frame: 24 Weeks
Population: The number of participants are analyzed by Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aggressive BP Lowering | Number of Participants With Adverse Events | With at leat one SAE | 10 participants |
| Aggressive BP Lowering | Number of Participants With Adverse Events | With AE due to the treatment | 5 participants |
| Aggressive BP Lowering | Number of Participants With Adverse Events | Withdrawn due to AE | 1 participants |
| Aggressive BP Lowering | Number of Participants With Adverse Events | Who died | 0 participants |
| Aggressive BP Lowering | Number of Participants With Adverse Events | With at least on AE | 51 participants |
| Modest BP Lowering | Number of Participants With Adverse Events | Who died | 0 participants |
| Modest BP Lowering | Number of Participants With Adverse Events | With at least on AE | 47 participants |
| Modest BP Lowering | Number of Participants With Adverse Events | With at leat one SAE | 8 participants |
| Modest BP Lowering | Number of Participants With Adverse Events | Withdrawn due to AE | 4 participants |
| Modest BP Lowering | Number of Participants With Adverse Events | With AE due to the treatment | 3 participants |
Secondary
Number of Participants With Cardiovascular Events From Screening to Week 24 in ITT Population.
Time frame: 24 weeks
Population: The number of participants are analyzed by ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aggressive BP Lowering | Number of Participants With Cardiovascular Events From Screening to Week 24 in ITT Population. | 14 participants |
| Modest BP Lowering | Number of Participants With Cardiovascular Events From Screening to Week 24 in ITT Population. | 14 participants |
Secondary
Number of Participants With Vascular Death From Screening to Week 24 in ITT Population.
Time frame: 24 Weeks
Population: The number of participants are analyzed by ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aggressive BP Lowering | Number of Participants With Vascular Death From Screening to Week 24 in ITT Population. | 0 participants |
| Modest BP Lowering | Number of Participants With Vascular Death From Screening to Week 24 in ITT Population. | 0 participants |
Secondary
The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI
Time frame: 24 weeks
Population: The Number of Participants are analyzed by ITT (Intent to treat) Population. ITT Population (Aggressive BP Lowering: 66, Modest BP Lowering: 63)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aggressive BP Lowering | The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI | Yes | 10 participants |
| Aggressive BP Lowering | The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI | No | 49 participants |
| Aggressive BP Lowering | The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI | Missing data | 7 participants |
| Modest BP Lowering | The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI | Yes | 5 participants |
| Modest BP Lowering | The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI | No | 47 participants |
| Modest BP Lowering | The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI | Missing data | 11 participants |
Secondary
Total Number of Cardiovascular Events Form Screening to Week 24 in ITT Population.
Time frame: 24 Week
Population: The number of participants are analyzed by ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aggressive BP Lowering | Total Number of Cardiovascular Events Form Screening to Week 24 in ITT Population. | 17 events |
| Modest BP Lowering | Total Number of Cardiovascular Events Form Screening to Week 24 in ITT Population. | 15 events |