Effects of Systemic Erythropoietin Therapy on Cerebral Autoregulation and Incidence of Delayed Ischemic Deficits in Patients With Aneurysmal Subarachnoid Hemorrhage
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- cerebral vasospasm indices (incidence, onset, severity) on transcranial Doppler
研究概览
简要总结
ABSTRACT:
Delayed ischemic deficits (DID) and strokes caused by low cerebral blood flow (CBF) are major sources of poor outcome following aneurysmal subarachnoid hemorrhage (SAH). DID are often accompanied by vasospasm and abnormalities in cerebrovascular autoregulation, an important reflex involved in the defense against low CBF. Assessment of vasospasm and impaired autoregulation can be conveniently measured non-invasively by use of transcranial Doppler (TCD) and the transient hyperaemic response test (THRT). Vasospasm and abnormalities in the THRT can predict those patients who are at risk of developing DID. In this study, the investigators wish to explore the neuroprotective and angiogenic effects of systemic erythropoietin (EPO) therapy on vasospasm and autoregulation following SAH, and examine whether any improvements translate into reduced incidences of DID and poor outcome. Eighty patients with SAH will be recruited over one year to receive three doses in the first week of either intravenous epoetin beta 30000 IU or placebo (0.9% saline) 50 ml/30 min as part of a randomized, double-blind, placebo-controlled trial. The investigators propose daily TCD assessment for detecting vasospasm and abnormal autoregulation. Outcome measures will examine the influence of EPO therapy on the incidence, severity, and duration of vasospasm, abnormal autoregulation, and DID.
PURPOSE:
This study is a randomized, double-blind, placebo-controlled clinical trial investigating the potentially beneficial effects of systemic recombinant human erythropoietin therapy (Epoetin beta, NeoRecormon®, Roche, 30000IU/50 ml/30 min, three times in the first week) on cerebral autoregulation and incidence of delayed ischemic deficits (DID) following aneurysmal subarachnoid haemorrhage (SAH).
HYPOTHESIS Systemic recombinant human erythropoietin therapy can be used safely following SAH to ameliorate vasospasm, improve cerebral autoregulation, reduce DID, and facilitate neurological recovery.
详细描述
BACKGROUND:
- Delayed ischaemia deficits in subarachnoid haemorrhage
Seven thousand patients suffer SAH each year within the UK with young adults (<55 years) being equally affected. Cerebral vasospasm and related cerebral ischemia are the major causes of delayed morbidity and mortality in patients who survive the initial SAH episode. Previous studies have revealed that immediate low cerebral blood flow (CBF) accompanies SAH, particularly in those in coma. However, for better grade patients the low CBF is often delayed and associated with cerebral vasospasm [Knuckey 1985]. Vasospasm often precedes the onset of DID which commonly occurs in the 2nd week after SAH [Knuckey 1985]. Autoregulation is the most accomplished reflex mechanism and reflects an intrinsic ability of the cerebral vessels to dilate in an attempt to maintain constant CBF in the face of poor cerebral perfusion. Following SAH, impairment of autoregulation affects prognosis [Lam 2000]. Indeed, daily assessment of autoregulation can help to identify patients at high risk of clinical deterioration [Smielewski 1997].
Autoregulation can be conveniently measured non-invasively from the bedside using transcranial Doppler (TCD). Direct measures of middle cerebral artery flow velocities (FV) are predictive of DID; elevated mean FV (>120cms/sec) and increased ratio of mFV between MCA and extracranial internal carotid artery (ICA) (Lindegaard ratio >3) being associated with cerebral vasospasm and higher incidence of adverse events [Lindegaard 1988]. The rapid increase of FV with time is also predictive, as is the relationship between FV and spontaneous changes in blood pressure (correlation index Mx) [Czosnyka 2000].
A more sophisticated measure of abnormal cerebrovascular haemodynamics involves the transient hyperaemic response test (THRT) [Giller 1991]. This is used routinely in our department where we have demonstrated a relationship between an abnormal THRT and clinical outcome following SAH [Lam 2000]. The THRT assesses the FV response to a manual carotid compression (Figure 1) and can be repeated within a few minutes providing a reliable and readily accessible method for assessing autoregulation. When THRT is used for day-to-day assessments for the same patient, this test can provide a valuable monitor of sequential changes in autoregulation. 2. Autoregulation after SAH
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Adult patients (>= 18 years)
- •Aneurysmal subarachnoid hemorrhage
排除标准
- •Uncontrolled systemic hypertension (systolic blood pressure > 220 mmHg)
- •Erythrocytosis vera
- •Concurrent erythropoietin therapy
- •Negative angiography
- •Subarachnoid hemorrhage more than 7 days
研究组 & 干预措施
A
30,000 units of erythropoietin beta in one vial; 3 vials as one set per patient
干预措施: erythropoietin beta (Drug)
结局指标
主要结局
cerebral vasospasm indices (incidence, onset, severity) on transcranial Doppler
时间窗: 14 days following aneurysmal subarachnoid hemorrhage
次要结局
- delayed ischemic neurological deficits(14 days following aneurysmal subarachnoid haemorrhage)
- disability measured with modified Rankin Scale, Glasgow Outcome Scale, National Institute of Stroke Scale(6 months following aneurysmal subarachnoid haemorrhage)