Intensive Blood Pressure Intervention in Stroke (IBIS) Trial
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Stroke event
研究概览
简要总结
The investigators propose to conduct a multicenter randomized controlled trial to test the effect of a systolic blood pressure target of less than 120 mmHg (intensive treatment) compared to a target of less than 140 mmHg (standard treatment) on the risk of total recurrent stroke (ischemic and hemorrhagic) among patients with a recent ischemic stroke. The study findings will help in the development of clinical guidelines for blood pressure management among patients with ischemic stroke and will have an important global impact on reducing stroke-related morbidity and mortality.
详细描述
Stroke is a leading cause of death and long-term disability worldwide, especially in the elderly population. Hypertension is a major risk factor for stroke. Previous clinical trials have documented that blood pressure (BP) reduction lowers the risk of incident and recurrent stroke. The Secondary Prevention of Small Subcortical Strokes (SPS3) trial reported that a systolic BP target of <130 mmHg was associated with a non-significant (p=0.08) 19% reduction in recurrent stroke compared to a systolic BP target of 130-149 mmHg among 3,020 patients with recent lacunar stroke. The Systolic Blood Pressure Intervention Trial (SPRINT) showed that a systolic BP target of <120 mmHg was associated with a 25% reduction in cardiovascular disease (CVD) and 27% reduction in all-cause mortality compared to a systolic BP target of <140 mmHg. In the SPRINT trial, patients with a history of stroke were excluded. Therefore, the optimal BP targets for the secondary prevention of stroke remain uncertain.
The investigators propose to conduct a multicenter randomized controlled trial to test the following hypotheses:
Primary Hypothesis: In patients with a recent ischemic stroke and a systolic BP ≥140 mmHg (or systolic BP ≥135 mmHg if on ≥1 antihypertensive medication), an intensive treatment strategy (a systolic BP target of <120 mmHg) will reduce the risk of total recurrent stroke (ischemic and hemorrhagic) events compared to a standard treatment strategy (a systolic BP target of <140 mmHg) over a follow-up period of up to four years. The targeted mean systolic BP difference between the two randomized groups will be ≥15 mmHg.
Subgroup Hypotheses: The effect of the intensive treatment strategy compared to the standard treatment strategy for the primary study outcome (total recurrent stroke) will be consistent in the following subgroups:
- Men and women
- Age <65 and ≥65 years at baseline
- Systolic BP levels at baseline (tertiles)
- Subtypes of ischemic stroke
- Diabetes and non-diabetes
- American College of Cardiology/America Heart Association atherosclerotic CVD risk scores (tertiles)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
The participants and study physicians/nurses will not be masked to patient randomization assignments due to different BP targets between the two randomization groups. However, study personnel who collect clinical outcome data at the baseline and follow-up examinations will be masked to patient assignments. The members of the Outcome Adjudication Committee will also be masked to patient randomization.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged ≥40 years
- •A history of symptomatic, MRI/CT-confirmed ischemic stroke (3-12 months since last acute onset)
- •Systolic BP ≥140 mmHg on 0 medication; 135-180 mmHg on 1 medication; 135-170 mmHg on up to 2 medications; 135-160 mmHg on up to 3 medications; or 135-150 mmHg on up to 4 medications
排除标准
- •Documented symptomatic intracranial and/or extracranial stenosis (≥50%), or asymptomatic intracranial and/or extracranial stenosis (≥70%)
- •Disabling stroke (modified Rankin score of ≥4)
- •Previous intracranial hemorrhage from a non-traumatic cause
- •Any symptoms of orthostatic hypotension during the standing BP measurement, or standing systolic BP <110 mmHg
- •Severe heart failure (NY Heart Association class III and IV) within the past six months or left ventricular ejection fraction (by any method) <35%
- •Any history of atrial fibrillation, ventricular aneurysm, or suspicion of cardioembolic pathology for stroke
- •Other specific cause of stroke identified by routine clinical care (e.g., arteritis, dissection, migraine/vasospasm, drug abuse)
- •Dialysis, eGFR <20 ml/min/1.73 m2, urine protein-to-creatinine ratio ≥1 g/g, or albumin-to-creatinine ratio ≥ 600 mg/g
- •Planned or probable revascularization (any angioplasty or vascular surgery) within three months after screening
- •A medical condition likely to limit survival to less than three years
- •A cancer diagnosed and treated within the past two years that, in the judgment of clinical study staff, would compromise a participant's ability to comply with the protocol and complete the trial (except non-melanoma skin cancer, early-stage prostate cancer, or localized breast cancer)
- •Any factors judged by the clinic team to be likely to limit adherence to the intervention
- •Failure to obtain informed consent from a participant
- •Currently participating in another intervention study
- •Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control
结局指标
主要结局
Stroke event
时间窗: Up to four years of follow-up
Stroke will be diagnosed based on clinical data, including symptoms and signs, computed tomography (CT), and/or magnetic resonance imaging (MRI) of the brain and large vessels.
次要结局
- Composite major CVD events(Up to four years of follow-up)
- Heart failure(Up to four years of follow-up)
- Dementia(Up to four years of follow-up)
- Myocardial infarction (MI)(Up to four years of follow-up)
- All-cause mortality(Up to four years of follow-up)
- Non-MI acute coronary syndrome(Up to four years of follow-up)