Perfusion and Antihypertensive Therapy in Acute Ischemic Stroke
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Change in Volume of Hypoperfused Tissue
研究概览
简要总结
The purpose of this study is to provide a description of blood flow changes in the brain after blood pressure lowering drugs are given. This information will be used by physicians to guide blood pressure lowering therapy in stroke patients in the future.
详细描述
Objective: To elucidate the inter-relationships between blood pressure (BP), cerebral blood flow (CBF) and oxygen metabolism in acute ischemic stroke in order to establish rational acute hypertension treatment thresholds.
Background: Management of acute hypertension in the first 48 hours after stroke is controversial and lends itself to competing rationales. Early reduction of BP may improve outcome by reducing the rate of hemorrhagic transformation and edema formation in early infarcts. Conversely, early BP reduction might reduce CBF and extend the infarct. Natural history studies have demonstrated that patients with higher BP at presentation have elevated early mortality rates, but causality has not been established. Consensus-based guidelines for acute BP management are not based on physiological data or sound evidence. The investigators propose to start addressing this clinical dilemma with a non-randomized controlled study of serial measurements of CBF and oxygen metabolism in acute stroke patients with 3 different levels of acute blood pressure representing 3 different potential treatment thresholds.
Hypothesis: The investigators hypothesize that the volume and severity of oligemia in at risk tissue will not increase with BP reduction in acute stroke patients.
Specific Aims:
- Determine the effect of mean arterial pressure (MAP) decreases on CBF.
- Determine the relationship between infarct volume change over time and MAP.
- Determine the frequency of hemorrhagic transformation and its relationship to MAP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Acute ischemic stroke within 72 hours of symptom onset. In cases where onset time can not be established, it will be considered to be the time when the patient was last known to be well.
- •18 years or older.
- •Patients with Partial Anterior Circulation Infarcts (PACI; Oxfordshire Stroke Classification Project; OSCP) will be included.
- •Patients with Posterior Circulation Infarcts (POCI) will be included only if there is evidence of cortical infarction in the territory of the posterior cerebral artery or its branches, including the occipital and mesial temporal lobes.
排除标准
- •Patients with a contraindication to the BP lowering protocol (i.e. known extracranial/intracranial arterial stenosis, high-grade stenotic valvular heart disease, or severe renal failure) will be ineligible, as will those with a definite indication for BP reduction (i.e. hypertensive encephalopathy, or aortic dissection).
- •Patients with contraindications to MRI will be excluded, including metallic implants and any past sensitivity to gadolinium contrast media.
- •Due to recent reports of nephrogenic systemic fibrosis associated with gadolinium exposure in individuals with pre-existing renal failure, patients with Creatinine > 160 μmol/l or Glomerular Filtration Rate (GFR) <60 ml/min will also be excluded.
- •Patients with renal artery stenosis will be excluded from this study, irrespective of renal function.
- •Due to the possibility that oxygen therapy may confound CBF measurements, patients requiring >4 lpm to keep Sp02 ≥92% by nasal cannulae will be excluded.
- •Patients with a suspected hemodynamic stroke mechanism will be ineligible. This will include patients with known or suspected hypotensive periods and/or a watershed territory of cerebral infarction seen on CT or MRI.
- •Due to the possibility of increased susceptibility to BP reduction in patients with raised intracerebral pressure (ICP), those with evidence of significant mass effect secondary to acute infarction, including any degree of midline shift and/or ventricular compression will be ineligible. For the same reason, patients with head and eye deviation or other clinical evidence of a Total Anterior Circulation Infarct (TACI; OSCP) will also be ineligible.
- •Due to technical difficulties associated with PWI in the posterior fossa, patients with brainstem and cerebellar strokes will be excluded.
- •Patients with known sensitivity to nitroglycerin/labetalol/adhesives in nitroglycerin patches/ACE inhibitors/Angiotensin Receptor Blockers will be excluded.
- •Amplification of the vasodilatory effects of topical nitroglycerin by phosphodiesterase inhibitors such as sildenafil or tadalafil can result in severe hypotension. Patients who have used either of these drugs within 12 h of initial assessment will therefore be excluded.
研究组 & 干预措施
Mean Arterial Pressure 100-120 mmHg
Patients with mean arterial pressure between 100-120 mmHg at the time of the perfusion weighted magnetic resonance imaging will be treated with sublingual 0.3 mg nitroglycerin. A repeat blood pressure would be assessed at 5min, 10min, 15min and 20 min of nitroglycerin administration. After a sustained drop of blood pressure (>10% of the baseline reading) as defined by two reading 5minutes apart, a perfusion weighted magnetic resonance imaging will be performed.
干预措施: Nitroglycerin (Drug)
Mean Arterial Pressure >120 mmHg
Patients with mean arterial pressure >120 mmHg at the time of the perfusion weighted magnetic resonance imaging will be treated with intravenous 10-20mg labetalol injection. A repeat blood pressure would be assessed at 5min, 10min, 15min and 20 min of labetalol injection. After a sustained drop in blood pressure (>10% of the baseline reading) as defined by two reading 5minutes apart, a perfusion weighted magnetic resonance imaging will be performed.
干预措施: Labetalol (Drug)
结局指标
主要结局
Change in Volume of Hypoperfused Tissue
时间窗: 15-30 minutes
Change in the volume of hypoperfused tissue, defined as that having a CBF \<19 ml/100g/min, between the acute and the post treatment initiation perfusion weighted scans.
次要结局
- Time-to-Treatment(15-30 minutes)
研究者
Ken Butcher
Assistant Professor
University of Alberta