The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 142
- 试验地点
- 2
- 主要终点
- Diffusion-weighted imaging (DWI) lesion frequency
研究概览
简要总结
The vast majority of intracerebral hemorrhage (ICH) patients present with elevated blood pressure(BP). Management of BP is controversial with two competing rationales. There is some evidence that hyperacute treatment may improve outcomes by reducing the rate of hematoma expansion. Physicians have been reluctant to reduce BP early after ICH onset, fearing reduced cerebral blood flow (CBF) will increase ischemia and increase the risk of further damage. Other confounding mediators to further ischemic injury following ICH include increased platelet activity, withdrawal of antithrombotic therapy, endothelial dysfunction, inflammation and hypercoagulability.
This study is phase II of the ICH-ADAPT study. The investigators hypothesize that aggressive antihypertensive therapy will alter the natural history of heamatoma growth, improving outcomes after Intracranial Hemorrhage (ICH). The previous phase I ICH-ADAPT study has established the safety of early BP treatment.
The investigators have designed a phase II study in which ICH patients are randomized to aggressive versus conservative BP treatment using a deferred consent procedure. An adaptive randomization will be used to treat BP to < 140 mmHg SBP or < 180 mmHg SBP. Treatment must be implemented as soon as possible after radiological confirmation of diagnosis. Antihypertensive therapy must begin within 6 hours of symptom onset. The patient will be re-imaged 24 hours later. The patient will have continuous non-invasive BP and heart rate(HR) monitoring for a minimum of 24 hours. Antihypertensive drug use and dosage will be recorded with BP and HR. Patients will be monitored regularly until study completion. MRI's will be done at 48 hours, day 7 and day 30. This imaging will help to detect ischemic changes that may occur. Blood will be collected at the same time as the MRI. Blood analysis will be done to possibly identify biomarkers that may be putative mediators of ischemic injury in ICH patients.
详细描述
Study Design: multi-centre randomized open-label, blinded-endpoint trial of two different BP management strategies. This study is being conducted in the Emergency Departments and Stroke Units of Canadian academic and non-academic centres.
Overall Aim and Hypothesis: The primary study aim is to assess the rate of ischemic lesion development in patients randomized to two different BP treatment strategies. The overall a priori hypothesis is that aggressive BP reduction will not be associated with ischemic injury after ICH.
Patients: Male and female patients will be recruited from Emergency Departments of participating hospitals. A total of 270 patients will be included over 3 years.
Baseline Data and Randomization: Demographics, Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores (both of which are part of routine stroke patient assessment), time of symptom onset and diagnostic CT scan will all be recorded. If the CT scan is completed within 6 hours of onset and confirms evidence of a primary ICH, patients will be randomized. Where patients are incompetent and surrogate decision makers are not immediately available, randomization will occur using a deferred consent procedure. Stroke risk factors, past medical history and medications, with emphasis on antihypertensives, as well as standard clinical blood work (complete blood count and coagulation profile) will be recorded after randomization in order to avoid delays to BP treatment.
Intervention - Blood Pressure Management Protocols:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Acute primary ICH demonstrated with CT scan, within 6 h of symptom onset.
- •Two systolic BP measurements ≥140 mmHg recorded >2 min apart to qualify for enrolment.
- •Onset ≤ 24 h prior to randomization
排除标准
- •Contraindication to BP reduction i.e., severe arterial stenosis or high-grade stenotic valvular heart disease
- •Indication for urgent BP reduction i.e., hypertensive encephalopathy, or aortic dissection
- •Definite evidence that the ICH is secondary to underlying cerebral or vascular pathology, i.e., AVM, aneurysm, tumour, trauma, vasculitis, or hemorrhagic transformation of an ischemic infarct
- •Previous ischemic stroke within 90 days of current event NB: Prior ICH is not an exclusion criterion
- •Patients with suspected secondary cause of ICH.
- •Planned surgical resection of hematoma NB: Extraventricular Drain placement is not an exclusion criterion
- •Contraindication to CT perfusion imaging (i.e. contrast allergy, metformin use or Creatinine >160 μmol/l)
- •Patients with pre-existing disability and dependence (defined as a pre-morbid modified Rankin Scale score ≥3) will be excluded
- •Patients with life expectancy <6 months due to pre-morbid conditions/terminal illness
- •Patients with known definite contraindications to MRI (pacemaker, ferrous metallic foreign body)
研究组 & 干预措施
Target systolic BP <140mmHg
Systolic blood pressure will be reduced to <140 mmHg within 1 hour of randomization.
干预措施: labetalol/hydralazine/enalapril (Drug)
Target systolic BP <180mmHg
Systolic blood pressure will be reduced, to <180 mmHg within 1 hour of randomization.
干预措施: labetalol/hydralazine/enalapril (Drug)
结局指标
主要结局
Diffusion-weighted imaging (DWI) lesion frequency
时间窗: 48 hours
次要结局
- Functional disability as assessed by the Modified Rankin Scale(90 days post randomization)
- Cumulative diffusion-weighted imaging (DWI) lesion frequency(30 days post randomization)
- Absolute hematoma growth(24 hours post randomization)