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Coagulation Activation by Hyperosmolar Agents in Intracranial Hypertension

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ClinicalTrials.gov Identifier: NCT03409237
Recruitment Status : Withdrawn (No participant enrolled. The human resources to perform the study also due to the COBID emegency)
First Posted : January 24, 2018
Last Update Posted : November 19, 2020
Sponsor:
Information provided by (Responsible Party):
Licia Iacoviello, Neuromed IRCCS

Brief Summary:

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.


Condition or disease Intervention/treatment
Intracranial Hypertension Cerebral Edema Drug: Mannitol Drug: Hypertonic saline solution

Detailed Description:

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.

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Study Type : Observational
Actual Enrollment : 0 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Evaluation of Coagulation Activation in Patients With Intracranial Hypertension After Treatment With Mannitol or Hypertonic Saline Solution.
Estimated Study Start Date : December 3, 2020
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Mannitol

Group/Cohort Intervention/treatment
Group 1
Mannitol 0.2-0.3 g/kg 4 times/day.
Drug: Mannitol
Therapy is administered according to the clinical gold standard and until reaching and maintaining serum sodium levels between 145 e 155 meq/l and an osmolarity <320.

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.
Drug: Hypertonic saline solution
Therapy is administered according to the clinical gold standard and until reaching and maintaining serum sodium levels between 145 e 155 meq/l and an osmolarity <320.

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.
Drug: Hypertonic saline solution
Therapy is administered according to the clinical gold standard and until reaching and maintaining serum sodium levels between 145 e 155 meq/l and an osmolarity <320.

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.
Drug: Hypertonic saline solution
Therapy is administered according to the clinical gold standard and until reaching and maintaining serum sodium levels between 145 e 155 meq/l and an osmolarity <320.




Primary Outcome Measures :
  1. Changes in coagulation parameters [ Time Frame: 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


Secondary Outcome Measures :
  1. Changes in inflammation markers [ Time Frame: Before osmotic therapy (time 0), after 12 hrs infusion (time 1) ]
    Inflammation markers such as C reactive protein, interleukin 6, P-selectin. E-selectin will be measured in plasma


Biospecimen Retention:   Samples Without DNA
Plasma, serum


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients (men and women) with cerebral edema / intracranial hypertension (CT / MRI neuroradiological diagnosis) on a non-traumatic basis with indication to osmotic therapy, treated on the basis of clinical and radiological evidence according to current treatment standards and meeting the inclusion criteria.
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03409237


Locations
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Italy
IRCCS INM Neuromed, Department of Epidemiology and Prevention
Pozzilli, IS, Italy, 86077
Sponsors and Collaborators
Neuromed IRCCS
Investigators
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Study Chair: Licia Iacoviello, MD, PhD IRCCS Neuromed
Principal Investigator: Fulvio Aloj, MD IRCCS Neuromed
Publications:

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Responsible Party: Licia Iacoviello, Professor, Neuromed IRCCS
ClinicalTrials.gov Identifier: NCT03409237    
Other Study ID Numbers: NMD-50/18
First Posted: January 24, 2018    Key Record Dates
Last Update Posted: November 19, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Intracranial Hypertension
Brain Edema
Hypertension
Vascular Diseases
Cardiovascular Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs