Milrinone Infusion for VAsospam Treatment in Subarachnoid hemoRrhage
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 370
- 试验地点
- 30
- 主要终点
- Proportion of patients with a good outcome at 3 months
研究概览
简要总结
Subarachnoid hemorrhage (SAH) is a frequent and severe disease. Mortality can reach 40%. The most frequent complication of SAH is arterial vasospasm, with estimated incidence as high as 70%. Vasospasm is responsible for cerebral ischemia leading to severe morbidity, poorer quality of life and increased mortality.
Intravenous Milrinone, because of vasodilatory properties could be a therapeutic option. We hypothesize that intravenous infusion of Milrinone will improve the neurological recovery of patients with vasospasm following aneurysmal SAH at 3 months.
This is a Phase III, multi-center, randomized, double-blinded, placebo-controlled study. The primary outcome will be the proportion of patients with a good outcome 3 months (defined as a modified rankin score ≤2).
详细描述
Subarachnoid hemorrhage (SAH) is relatively frequent, accounting for 5% of strokes, and affects a relatively young population. It is essentially caused by cerebral aneurysm rupture. Mortality can reach 40%. The most frequent complication of SAH is arterial vasospasm, with estimated incidence as high as 70%. Vasospasm is responsible for cerebral ischemia, delayed or not, which in turn is responsible for severe morbidity (neurological deficit, neuro psychiatric disorders...), poorer quality of life (institutionalization, inability to return to work ...) and increased mortality.
The pathophysiology of vasospasm is complex, multifactorial and far from being fully understood. Many drugs have been studied in the treatment of symptomatic vasospasm but none has really proven its efficacy. Milrinone is proposed for the treatment of cerebral vasospasm, either as intra-arterial injection (during angiography) or intravenously using continuous infusion. Indeed, among new vasospasm's treatments, Milrinone seems to have good angiographic and clinical results. There is no randomized controlled trials evaluating Milrinone for preventive and/or curative treatment of cerebral vasospasm following aneurysmal SAH. The literature is made only of clinical cases, cases series with angiographic studies or interventional studies not controlled and with no more than 10 patients.
Thus we hypothesize that the intravenous infusion of Milrinone will improve the neurological recovery of patients with vasospasm following aneurysmal SAH at 3 months.
Adult patients, hospitalized for a vasospasm complicating subarachnoid hemorrhage secondary to intracranial aneurysm rupture will be included and randomized within 6 hours of the CT-scanner confirming the vasospasm diagnosis to receive either the study drug (milrinione, a 0,1 mg/kg bolus followed by a 1 μg/kg/min perfusion) or placebo (saline, with a bolus and a continuous infusion). Study drug administration will be formalized (minimum duration 48 hours, maximum duration 14 days).The primary endpoint will be the proportion of patients with a good outcome 3 months (defined as a modified rankin score ≤2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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 hospitalized for aneurysmal SAH
- •First episode of vasospasm, with a diagnosis confirmed on cerebral arterial CT-scanner
- •Delay between diagnosis of vasospasm (done by CT-scanner) and inclusion ≤6 hours
- •Informed consent from a legal representative, or emergency procedure
排除标准
- •Initial Glasgow score at 3 with a bilateral mydriasis
- •Moribund patient
- •Contraindication to Milrinone (notably obstructive cardiomyopathy…)
- •Cerebral infarction in the vasospasm area already present on the CT-scanner at the time of diagnosis (lack of expected benefit of treatment in this case according to medical judgement)
- •Cardiac failure requiring inotrope administration at the time of randomisation
- •Uncontrolled elevated intra-cranial pressure (i.e. ICP>25 mmHg for more than 20 minutes)
- •Patient with flutter or cardiac arrhythmia (atrial fibrillation) poorly tolerated
- •Major metabolic disturbance (uncorrected hypokalaemia <3 mmol/L)
- •Non-affiliation to French health care coverage,
- •Pregnant, breastfeeding or parturient woman
- •Adult deprived of their liberty by judicial or administrative decision
- •Adult under compulsory psychiatric care
- •Adult patient protected under the law (guardianship or trusteeship)
- •Inclusion in an interventional study using Milrinone, or evaluating a treatment of cerebral vasospasm or with the same primary endpoint (mRS at 3 months).
研究组 & 干预措施
Milrinone
The patients randomized to this arm will have Milrinone (Laboratoires STRAGEN, France)
干预措施: Milrinone 1 Mg/mL Solution for Injection (Drug)
Placebo
The patients randomized to this arm will have Saline solution
干预措施: Saline solution for injection (Drug)
结局指标
主要结局
Proportion of patients with a good outcome at 3 months
时间窗: 3 months
modified Rankin score ≤2 (0 = No symptoms, 1 = No significant disability. Able to carry out all usual activities, despite some symptoms, 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability. Requires some help, but able to walk unassisted, 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent, 6 = Death)
次要结局
- Mortality rates in intensive care and in hospital(up to 6 months)
- Modified Rankin Score at 6 months(6 months)
- Glasgow outcome scale Extended at 3 and 6 months(up to 6 months)
- EQ-5D(up to 6 months)
- Evaluation of the radiologic effectiveness of the treatment(3 months)
- Evaluation of the hemodynamic tolerance of the treatment(24 hours)
- Evaluation of the metabolic tolerance of the treatment(up to 14 days)
- cerebral artery flow velocities(H0, H+2, H24+/-12h, H48+/-12h)
- Length of stay in the intensive care unit and in the hospital(3 months)
- live patient rate(3 months and 6 months)
- Modified Rankin Score at 3 and 6 months(3 and 6 months)
- Evaluation of the radiologic effectiveness of the treatment(up to 14 days)
- Describe the number of therapeutic arteriographies(Day 14)