The Effect of Remote Ischemic Conditioning on Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Prospective, Randomized, Patient-assessor Blinded, Sham-controlled Pilot Study Investigating Effect on Clinical Outcome.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Clinical outcome after 6 months measured by modified Rankin scale score (0-6, Higher score indicates worse outcome)
研究概览
简要总结
The goal of this clinical trial is to examine the effect of limb occlusion therapy (remote ischemic conditioning, RIC) in subjects with aneurysmal subarachnoid hemorrhage.
The main question it aims to answer is whether RIC can improve long-term recovery in participants with aneurysmal subarachnoid hemorrhage.
Researchers will compare levels of functional independence in participants in the RIC-group to participants in the sham-group.
详细描述
Aneurysmal subarachnoid hemorrhage (aSAH) is one of the most devastating types of stroke. Half of the patients die during the acute ictus, and those who survive have a poor prognosis as 20-30% are disabled or eventually die from the disease. In the acute phase after aSAH, the most devastating complication is rebleeding, whereas in the late phase, delayed cerebral ischemia (DCI) is another feared complication, associated with high morbidity and mortality. Symptoms of DCI occur in 30 % of patients and 15-20 % of patients will develop a disabling stroke due to DCI. DCI typically occurs between days 4 and 14 after the initial bleeding. The cause of DCI is not fully understood. Cerebral vasospasms (CVS) are commonly seen on angiography in the first 4-14 days after initial bleeding, and have been linked to late onset of symptoms of focal ischaemia since the 60s. Modern research suggests that the pathophysiology is multifactorial, but CVS is still thought to be a major contributor. Other contributing factors are thought to be microthrombosis, microvascular spasm, oxidative stress, cortically spreading depolarizations, cell death, breakdown of blood-brain barrier, among others. Treatment with nimodipine is standard-of-care and is the only pharmacological intervention that has been shown to improve outcome in aSAH patients, although it has no impact on large-vessel CVS[.
The need for developing effective methods for prevention or treatment of DCI persists, and an effective prophylactic treatment may have a large impact on the general outcome of aSAH.
Ischemic conditioning is a potent activator of endogenous protection against ischemic injury. RIC can be applied as repeated short-lasting ischemia in a distant tissue that results in protection against subsequent long-lasting ischemic injury in the target organ. This protection can be applied prior to or during a prolonged ischemic event as remote ischemic preconditioning (RIPreC) and perconditioning (RIPerC), respectively.
RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion. RIC activates several protective mechanisms, through humoral and neural pathways and shows promise in the setting of acute stroke.
Inflammation initiated by cerebral ischemia can contribute to secondary brain injury and is correlated with poor outcome. Following ischemia there is a harmful excess leukocyte infiltration in the brain parenchyma, and in experimental studies on aSAH, pharmacological inhibition of cytokines has been associated with improved outcome. RIC has been demonstrated to reduce inflammation and downregulate inflammatory markers. In addition, RIC has protective effects on cerebral endothelial function and induces vasodilation, increasing cerebral blood flow (CBF).
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
- Double (Participant, Outcomes Assessor)
盲法说明
Outcomes assessors are recruited from another department, and have not been involved with subjects prior to the telephone interview. Participants and outcome assessors are blinded to subject intervention.
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
- •Aneurysmal subarachnoid hemorrhage confirmed by computed tomography (CT) with aneurysm origin confirmed by computed tomography angiography (CTA) or digital subtraction angiography (DSA)
- •Aneurysmal subarachnoid hemorrhage symptom-onset ≤ 3 days
- •Aneurysm protected by clipping or coiling
- •Independent in daily living before symptom onset (mRS ≤ 2)
排除标准
- •Subarachnoid hemorrhage caused by a lesion other than cerebral aneurysm
- •Symptomatic vasospasm at the time of enrollment
- •Previous cerebral lesion e.g. symptomatic cerebral infarction (>2cm), multiple sclerosis, symptomatic intracerebral hemorrhage, tumour, prior neurosurgery (excluding prior clipping or coiling of cold aneurysms without complications).
- •History of severe peripheral vascular disease or signs of severe peripheral vascular disease on physical examination
- •History of deep vein thrombosis or signs of deep vein thrombosis on physical examination
- •Kidney involvement or prior kidney disease with an estimated glomerular filtration rate (eGFR) below safe levels for contrast infusion in relation to CT-perfusion.
- •Pregnancy (Women of child-bearing age will have serum-Humane Choriogonadotropine taken prior to final inclusion. If pregnancy cannot be ruled out,the patient can't be included. Women with a safe birth control method will be encouraged to use this method during the entire period of active treatment.)
- •Concomitant other acute life-threatening medical or surgical condition
结局指标
主要结局
Clinical outcome after 6 months measured by modified Rankin scale score (0-6, Higher score indicates worse outcome)
时间窗: Assessed 6 months after initial aneurysm rupture.
Assessed by telephone interview. Patient assessor is blinded to intervention
次要结局
- Clinical outcome after 14 days measured by modified Rankin scale score (0-6, Higher score indicates worse outcome)(14 days after initial hemorrhage.)
- Mortality after 3 months(Assessed at 3 months post initial hemorrhage)
- Mortality after 12 months(Assessed at 12 months post initial hemorrhage)
- Difference in Infarct growth(MRI performed 4-6 weeks after initial hemorrhage.)
- Occurrence of delayed cerebral ischemia(Within first 14 days after initial hemorrhage.)
- Presence of angiographic vasospasm on CT angiography baseline vs 8-day scan(8-9 days post initial hemorrhage.)
研究者
Grethe Andersen
Professor, Consultant Neurologist, MD
Aarhus University Hospital