Coagulation Activation by Hyperosmolar Agents in Intracranial Hypertension

November 17, 2020 updated by: Licia Iacoviello, Neuromed IRCCS

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • IS
      • Pozzilli, IS, Italy, 86077
        • IRCCS INM Neuromed, Department of Epidemiology and Prevention

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Before osmotic therapy (time 0), after 12 hrs infusion (time 1)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Before osmotic therapy (time 0), after 12 hrs infusion (time 1)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neuromed IRCCS

Investigators

  • Study Chair: licia Iacoviello, MD, PhD, IRCCS Neuromed
  • Principal Investigator: Fulvio Aloj, MD, IRCCS Neuromed

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 3, 2020

Primary Completion (Anticipated)

July 1, 2021

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

January 9, 2018

First Submitted That Met QC Criteria

January 17, 2018

First Posted (Actual)

January 24, 2018

Study Record Updates

Last Update Posted (Actual)

November 19, 2020

Last Update Submitted That Met QC Criteria

November 17, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NMD-50/18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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