Induced Hypertension in Acute PRogrESsive Perforating Artery Stroke Using Peripheral Dilute noREpinephrine
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 358
- 试验地点
- 1
- 主要终点
- modified Rankin Scale (mRS)
研究概览
简要总结
PRESSURE is a multicenter, prospective, randomized, open, blinded end-point assessed (PROBE) trial, that aims to evaluate the efficacy and safety of drug-induced hypertension using peripheral dilute norepinephrine, in patients with acute ischemic stroke in a perforating artery territory and experiencing early neurological deterioration.
详细描述
Perforating artery strokes represent 25% of all ischemic strokes and is a well-known cause of progressive symptoms : 12 to 36% of cases experience early neurological deterioration in hours or days after stroke onset. A possible mechanism is hypoperfusion due to lack of a rapid development of collateral flow because of the terminal distribution of perforating arteries. Moreover, arterioles are maximally dilated within penumbra region, resulting in a cerebral autoregulation failure and a passive dependence of cerebral blood flow on arterial pressure. Thus, induced-hypertension therapy by using vasopressive agents is an attractive therapy to increase the cerebral perfusion pressure and therefore restore blood flow in the ischemic penumbra.
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
- Single (Participant)
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
- •Acute ischemic stroke < 72 h in a perforating artery territory on brain MRI
- •Early neurological deterioration or fluctuation, attested by the neurologist in charge, defined by a ≥ 3-point increase in global NIHSS score OR a 2-point increase on motor or ataxia score, whether this deterioration is transient or permanent.
- •Time between early neurological deterioration and randomization < 6 hours
- •Age ≥ 18 years
- •Contraception required in women of childbearing potential (Intra-uterine device, hormonal contraception associated with inhibition of ovulation (combined or progestogen-only; oral, intravaginal or transdermal), Female Sterilization, Vasectomised partner, sexual abstinence)
- •Beneficiary of a health insurance system
排除标准
- •- Pre-Stroke Modified Rankin Score > 3
- •Contraindication to brain Magnetic Resonance Imaging (MRI)
- •High risk of intracerebral hemorrhage:
- •Cerebral microbleeds ≥ 10
- •Non traumatic focal superficial siderosis
- •Hemorrhagic transformation of the present ischemic stroke
- •Previous history of intracerebral hemorrhage (symptomatic or asymptomatic identified on brain MRI)
- •Intracranial vascular malformation or tumor with suspected risk of rupture or bleeding
- •Prior intravenous thrombolysis < 24 hours
- •Requirement for anticoagulation in the first 7 days after randomization
- •Systolic blood pressure (SBP) > 180mmHG and/or mean arterial pressure (MAP) ≥ 110mmHG at inclusion
- •Large artery atherosclerosis (ipsilateral atherosclerotic stenosis > 50%), intra and extracranial dissection, or cardio-embolic stroke mechanisms
- •Drugs with important interactions with norepinephrine: monoamine oxidase inhibitors (including reversible, non-selective agents such as linezolid), tricyclic antidepressants, entacapone.
- •Pregnancy or breastfeeding
研究组 & 干预措施
Induced hypertension using norepinephrine
Standard care and peripheral intravenous norepinephrine. Norepinephrine (dilution: 10µg/ml, initial dose: 0.04µg/kg/min) will be titrated until MAP is between 110 and 120mmHG (with a maximal systolic blood pressure of 210mmHG) Gradually decrease of norepinephrine will start after 24h of NIHSS stabilization.
Standard care includes antithrombotic treatments according to the physician's choice and ESO recommendations
干预措施: Peripheral intravenous norepinephrine (Drug)
结局指标
主要结局
modified Rankin Scale (mRS)
时间窗: Day 90
Functional independence defined by modified Rankin scale 0-2 or return to pre-stroke modified Rankin scale, assessed at 90 days. The assessment of the clinical outcome at 90 (±15) days will be conducted by an independent qualified assessor (blinded to patient treatment allocation). The minimal value of the modified Rankin Scale is 0 (best outcome) and the maximum value is 6 (worst outcome).
次要结局
- NIHSS Score(Day 7)
- Mortality(Day 90)
- Proportion of patients presenting Congestive heart failure(Day 7)
- Proportion of patients presenting Acute coronary syndrome(Day 7)
- modified Rankin Scale (mRS)(Day 90)
- Hospital Anxiety and Depression Scale(Day 90)
- Primary Care PTSD Screen for DSM-5 (PC-PTSD-5)(Day 90)
- Proportion of patients presenting Tachyarrhythmia(Day 7)