Ischemic Stroke
Conditions
Keywords
Ischemic stroke, Hypertension, Antihypertensive Agents, Randomized Controlled Trial
Brief summary
This randomized trial tests the effect of early blood pressure reduction on major disability and death among patients with acute ischemic stroke in china.
Detailed description
We designed a randomized controlled clinical trial to test: * The effectiveness of blood pressure reduction among patients with acute ischemic stroke (within 48 hours of onset) on the primary outcome, a combination of death within 14 days after randomization and dependency (modified Rankin scale ≥3) at 14 day or at the time of discharge, if that occurred before 14 days. * The effectiveness of blood pressure reduction among patients with acute ischemic stroke (within 48-hours of onset) on secondary outcomes: * Combination of all-cause mortality and dependency over 3, 12, and 24 months of follow-up * Combined vascular disease events over 3, 12, and 24 months of follow-up (vascular deaths, non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, hospitalized or treated angina, hospitalized or treated congestive heart failure, and hospitalized or treated peripheral arterial disease) * Recurrent fatal and non-fatal stroke over 3, 12, and 24 months of follow-up * Neurological functional status measured by NIH Stroke Score and modified Rankin scale at 14 day or discharge after randomization, and over 3, 12, and 24 months of follow-up * All-cause mortality over 3, 12, and 24 months of follow-up * Duration of initial hospitalization * Changes in systolic and diastolic blood pressure within 24 hours and over 7 days, and 14 days
Interventions
OTHERActive antihypertensive treatment
Initial antihypertensive treatment with angiotensin-converting enzyme inhibitors (Enalapril) and/or calcium channel blockers as second line medication; and/or diuretics as third line medications. Based on patients' baseline BP level, the first-line medication (intravenous Enalapril) can be used alone, or in combination with second-line medication (calcium channel blocker), and third-line medication (diuretics) to achieve the target systolic BP lowering by 10% to 25% within the first 24 hours after randomization and to achieve systolic BP below 140 mm Hg and diastolic BP below 90 mm Hg and maintain this BP level afterwards during the hospitalization.
Sponsors
Soochow University
Tulane University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥22 years * Ischemic stroke onset within 48 hours confirmed by imaging (CT scan or MRI) study * Systolic BP≥140 and \<220 mm Hg and diastolic BP≥80 mm Hg * No contraindications to antihypertensive treatment * Able and willing to sign informed consent by patients or their direct family members
Exclusion criteria
* Individuals with hemorrhagic stroke * Individuals with severe heart failure (NY Heart Association class III and IV), myocardial infarction, unstable angina, aortic dissection and cerebrovascular stenosis * Individuals in a deep coma * Individuals with resistant hypertension \[systolic BP ≥170 mm Hg despite use of 4 or more antihypertensive medications for half a year or longer\] * Intravenous thrombolytic therapy (such as intravenous rtPA) * Individuals who are unable to participate in follow-up examination * Current pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A Combination of Death Within 14 Days After Randomization and Major Disability at 14 Days or at Hospital Discharge if Earlier Than 14 Days. | 2 weeks | Major disability was defined as a score of 3 to 5 on the modified Rankin Scale at 14 days after randomization. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 3 months | Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information on clinical deaths will be obtained. |
| Recurrent Stroke | 3 months | Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of recurrent stroke will be collected. |
| Other Vascular Events | 3 months | Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of vascular events, such as myocardial infarction, will be collected. |
| A Combination of All-cause Mortality and Major Disability at the 3-month Post-treatment Follow-up. | 3 months | Major disability was defined as a score of 3 to 5 on the modified Rankin Scale at 3 months after randomization. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death |
| Cognitive Function (the Mini-Mental State Examination) | Three months | Cognitive function was measured by the Mini-Mental State Examination at 3 months after randomization. The MMSE contains 20 items that test cognitive performance in domains including orientation, registration, attention and calculation, recall, language, and visual construction. MMSE scores were divided into three ordinal categories: 24-30 (no cognitive impairment), 19-23 (mild cognitive impairment), and 0-17 (severe cognitive impairment). |
| Cognitive Function (Montreal Cognitive Assessment) | Three months | Cognitive function was measured by Montreal Cognitive Assessment at 3 months after randomization. The MoCA is a 30-item test that evaluates the following seven cognitive domains: visuospatial/executive functions, naming, memory, attention, language, abstraction, and orientation. One point is added for participants with education \<12 years. Scores on the MoCA range from 0 to 30 and cognitive impairment was defined as a score of \<26. |
| Quality of Life | 3 months | Due to limited funding, quality of life data were not collected. |
| Long-term Neurological and Functional Status | Three months | Those patients who were still alive at hospital discharge were contacted by telephone to set up a follow-up clinical visit. Neurological function was assessed by the modified Rankin scale at the 3-month post-treatment follow-up visit. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death. Major disability was defined as a score of 3 to 5 on the modified Rankin Scale. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Antihypertensive Treatment Active antihypertensive treatment
Active antihypertensive treatment: Initial antihypertensive treatment with angiotensin-converting enzyme inhibitors (Enalapril) and/or calcium channel blockers as second line medication; and/or diuretics as third line medications. Based on patients' baseline BP level, the first-line medication (intravenous Enalapril) can be used alone, or in combination with second-line medication (calcium channel blocker), and third-line medication (diuretics) to achieve the target systolic BP lowering by 10% to 25% within the first 24 hours after randomization and to achieve systolic BP below 140 mm Hg and diastolic BP below 90 mm Hg and maintain this BP level afterwards during the hospitalization. | 2,038 |
| Usual Care Discontinue all home BP medications. | 2,033 |
| Total | 4,071 |
Baseline characteristics
| Characteristic | Usual Care | Total | Active Antihypertensive Treatment |
|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 11 | 62.0 years STANDARD_DEVIATION 10.9 | 62.1 years STANDARD_DEVIATION 10.8 |
| Race/Ethnicity, Customized Asian | 2033 participants | 4071 participants | 2038 participants |
| Region of Enrollment China | 2033 participants | 4071 participants | 2038 participants |
| Sex: Female, Male Female | 1287 Participants | 2604 Participants | 1317 Participants |
| Sex: Female, Male Male | 746 Participants | 1467 Participants | 721 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2,038 | 0 / 2,033 |
| serious Total, serious adverse events | 0 / 2,038 | 0 / 2,033 |
Outcome results
Primary
A Combination of Death Within 14 Days After Randomization and Major Disability at 14 Days or at Hospital Discharge if Earlier Than 14 Days.
Major disability was defined as a score of 3 to 5 on the modified Rankin Scale at 14 days after randomization. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death.
Time frame: 2 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care | A Combination of Death Within 14 Days After Randomization and Major Disability at 14 Days or at Hospital Discharge if Earlier Than 14 Days. | 681 participants |
| Active Antihypertensive Treatment | A Combination of Death Within 14 Days After Randomization and Major Disability at 14 Days or at Hospital Discharge if Earlier Than 14 Days. | 683 participants |
Secondary
A Combination of All-cause Mortality and Major Disability at the 3-month Post-treatment Follow-up.
Major disability was defined as a score of 3 to 5 on the modified Rankin Scale at 3 months after randomization. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death
Time frame: 3 months
Population: All participants examined at 3-month posttreatment follow-up visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | A Combination of All-cause Mortality and Major Disability at the 3-month Post-treatment Follow-up. | 502 Participants |
| Active Antihypertensive Treatment | A Combination of All-cause Mortality and Major Disability at the 3-month Post-treatment Follow-up. | 500 Participants |
Secondary
Cognitive Function (Montreal Cognitive Assessment)
Cognitive function was measured by Montreal Cognitive Assessment at 3 months after randomization. The MoCA is a 30-item test that evaluates the following seven cognitive domains: visuospatial/executive functions, naming, memory, attention, language, abstraction, and orientation. One point is added for participants with education \<12 years. Scores on the MoCA range from 0 to 30 and cognitive impairment was defined as a score of \<26.
Time frame: Three months
Population: In a pre-planned ancillary study, 660 participants were systemically selected prior to randomization for cognitive function assessment. At the 3-month visit, 15 patients were lost to follow-up and 7 patients were deceased. A total of 638 participants who completed the cognitive function tests were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Cognitive Function (Montreal Cognitive Assessment) | 22 MoCA score |
| Active Antihypertensive Treatment | Cognitive Function (Montreal Cognitive Assessment) | 22 MoCA score |
Secondary
Cognitive Function (the Mini-Mental State Examination)
Cognitive function was measured by the Mini-Mental State Examination at 3 months after randomization. The MMSE contains 20 items that test cognitive performance in domains including orientation, registration, attention and calculation, recall, language, and visual construction. MMSE scores were divided into three ordinal categories: 24-30 (no cognitive impairment), 19-23 (mild cognitive impairment), and 0-17 (severe cognitive impairment).
Time frame: Three months
Population: In a pre-planned ancillary study, 660 participants were systemically selected prior to randomization for cognitive function assessment. At the 3-month visit, 15 patients were lost to follow-up and 7 patients were deceased. A total of 638 participants who completed the cognitive function tests were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Cognitive Function (the Mini-Mental State Examination) | 26 MMSE score |
| Active Antihypertensive Treatment | Cognitive Function (the Mini-Mental State Examination) | 26 MMSE score |
Secondary
Long-term Neurological and Functional Status
Those patients who were still alive at hospital discharge were contacted by telephone to set up a follow-up clinical visit. Neurological function was assessed by the modified Rankin scale at the 3-month post-treatment follow-up visit. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death. Major disability was defined as a score of 3 to 5 on the modified Rankin Scale.
Time frame: Three months
Population: Those patients who are still alive and followed at 3-Month posttreatment follow-up visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Long-term Neurological and Functional Status | 1.0 Score on modified Rankin scale |
| Active Antihypertensive Treatment | Long-term Neurological and Functional Status | 1.0 Score on modified Rankin scale |
Secondary
Mortality
Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information on clinical deaths will be obtained.
Time frame: 3 months
Population: All participants followed at 3-month posttreatment follow-up visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care | Mortality | 68 participants |
| Active Antihypertensive Treatment | Mortality | 54 participants |
Secondary
Other Vascular Events
Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of vascular events, such as myocardial infarction, will be collected.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care | Other Vascular Events | 59 participants |
| Active Antihypertensive Treatment | Other Vascular Events | 48 participants |
Secondary
Quality of Life
Due to limited funding, quality of life data were not collected.
Time frame: 3 months
Secondary
Recurrent Stroke
Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of recurrent stroke will be collected.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care | Recurrent Stroke | 28 participants |
| Active Antihypertensive Treatment | Recurrent Stroke | 43 participants |