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临床试验/NCT03409237
NCT03409237撤回不适用

Evaluation of Coagulation Activation in Patients With Intracranial Hypertension After Treatment With Mannitol or Hypertonic Saline Solution.

Neuromed IRCCS1 个研究点 分布在 1 个国家开始时间: 2020年12月3日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
不适用
状态
撤回
发起方
试验地点
1
主要终点
Changes in coagulation parameters

研究概览

简要总结

Osmotherapy consists in the therapeutic use of osmotically active substances with the aim of reducing the volume and therefore the intracranial pressure. It therefore represents an essential component in the clinical management of cerebral edema and intracranial hypertension, whether they are a consequence of head trauma, ischemic or hemorrhagic stroke, and neoplasm or neurosurgical procedures.

The current study aims at evaluating in vivo the effects on haemostasis parameters of hypertonic saline solutions at different concentration, as compared to mannitol, in patients with neuroradiological signs (CT / MRI) of cerebral edema / non-traumatic intracranial hypertension.

详细描述

Osmotherapy is commonly used in the treatment of intracranial hypertension (ICH) due to a variety of causes, including head trauma, intracranial neoplasia, infection or hemorrhage, and status epilepticus. The principle goal of osmotherapy is to shift fluid from the intracellular into the extracellular compartment using intravenous hyperosmolar agents, thereby reducing brain edema and improving cerebral perfusion pressure. Although 10-20% mannitol is considered the gold standard hyperosmolar agent in the treatment of ICH, mannitol-induced osmotic diuresis may cause hypovolemia and reduction in cerebral perfusion pressure. In recent years, 3.0-7.5% hypertonic saline (HTS) has gained popularity in the treatment of ICH as it has less pronounced diuretic effects and therefore does not cause hypovolemia. Indeed, in the face of hypovolemic shock and traumatic brain injury, HTS provides the advantage of volume expansion, restoring adequate cerebral perfusion pressures, and reducing brain edema, which makes it superior to mannitol in trauma patients with shock.

Both mannitol and HTS have been shown to interfere with whole blood coagulation and platelet function. This is in part due to dilutional coagulopathy. Furthermore, 7.2% HTS may directly disturb both fibrin formation and platelet function, and mannitol may interfere with coagulation by reducing clot strength. In addition, hyperosmolarity is supposed to lead to impairment of both whole blood coagulation and platelet function . In consequence, the safety of using these agents in patients with ICH and intracranial hemorrhage remains unclear. Previous in vitro studies in humans have demonstrated anticoagulant effects of both mannitol and HTS, although one clinical study failed to demonstrate any negative effect on hemostasis using either solution in patients undergoing elective intracranial surgery. However, in vivo studies in a clinical setting are lacking.

研究设计

研究类型
Observational
观察模型
Case Control
时间视角
Prospective

入排标准

年龄范围
18 Years 至 80 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Indication to osmotic therapy for cerebral edema / non-traumatic intracranial hypertension
  • Age 18 - 80 years
  • Body temperature between 35.5 ° C and 37.5 °C

排除标准

  • Congenital or acquired disorders of hemostasis
  • Clinical history of abnormal bleeding
  • Hematologic or Renal diseases (acute or chronic renal failure II-III stage)
  • Chronic or recent therapy with antiplatelet and/or anticoagulants
  • Taking corticosteroids or nonsteroidal anti-inflammatory drugs (less than 4 weeks)
  • Administration of macromolecular vascular filling solutions (less than 4 weeks)
  • History of recent venous / arterial thromboembolic disease (less than three months)
  • Moderate-severe liver dysfunction
  • Anemia (hb <10 mg/dl)
  • Recent transfusions (less than three months)
  • Hyponatremia (Na <135 meq/l)
  • Hypernatremia (Na> 155 meq/l)

研究组 & 干预措施

Group 1

Mannitol 0.2-0.3 g/kg 4 times/day.

干预措施: Mannitol (Drug)

Group 2

Hypertonic saline solution 3%. Continous infusion of 0,5 ml/kg/h. If necessary a loading dose of 2,5 ml/kg is administered.

干预措施: Hypertonic saline solution (Drug)

Group 3

Hypertonic solution saline 4%. Continous infusion of 0,5 ml/kg/h. If necessary a loading dose of 2,5 ml/kg is administered.

干预措施: Hypertonic saline solution (Drug)

Group 4

Hypertonic saline solution 7%. Continous infusion of 0,5 ml/kg/h. If necessary a loading dose of 2,5 ml/kg is administered.

干预措施: Hypertonic saline solution (Drug)

结局指标

主要结局

Changes in coagulation parameters

时间窗: Before osmotic therapy (time 0), after 12 hrs infusion (time 1)

Coagulation parameters such as thrombin and prothrombin time, fibrinogen, thrombin generation time will be measured in plasma by ELISA test or on whole blood by thromboelastography

次要结局

  • Changes in inflammation markers(Before osmotic therapy (time 0), after 12 hrs infusion (time 1))

研究者

发起方
Neuromed IRCCS
申办方类型
Other
责任方
Principal Investigator
主要研究者

Licia Iacoviello

Professor

Neuromed IRCCS

研究点 (1)

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