Coagulation Activation by Hyperosmolar Agents in Intracranial Hypertension

NCT03409237 | Withdrawn

• 1 other identifier: NMD-50/18
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Intracranial Hypertension; Cerebral Edema

Outcome Measures

Primary Outcomes (1)

• Changes in coagulation parameters

  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 Outcomes (1)

• Changes in inflammation markers

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

Study Arms (4)

Group 1

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

Drug: Mannitol

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

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

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

Interventions

Mannitol DRUG

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 1

Hypertonic saline solution DRUG

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; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Neuromed IRCCS: lead

Study Sites (1)

IRCCS INM Neuromed, Department of Epidemiology and Prevention

Pozzilli, IS, 86077, Italy

Location

Related Publications (18)

• Torre-Healy A, Marko NF, Weil RJ. Hyperosmolar therapy for intracranial hypertension. Neurocrit Care. 2012 Aug;17(1):117-30. doi: 10.1007/s12028-011-9649-x.

  PMID: 22090171 BACKGROUND

• Ropper AH. Hyperosmolar therapy for raised intracranial pressure. N Engl J Med. 2012 Aug 23;367(8):746-52. doi: 10.1056/NEJMct1206321. No abstract available.

  PMID: 22913684 BACKGROUND

• Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma. 2007;24 Suppl 1:S14-20. doi: 10.1089/neu.2007.9994. No abstract available.

  PMID: 17511539 BACKGROUND

• White H, Cook D, Venkatesh B. The use of hypertonic saline for treating intracranial hypertension after traumatic brain injury. Anesth Analg. 2006 Jun;102(6):1836-46. doi: 10.1213/01.ane.0000217208.51017.56.

  PMID: 16717334 BACKGROUND

• Prough DS, Whitley JM, Taylor CL, Deal DD, DeWitt DS. Regional cerebral blood flow following resuscitation from hemorrhagic shock with hypertonic saline. Influence of a subdural mass. Anesthesiology. 1991 Aug;75(2):319-27. doi: 10.1097/00000542-199108000-00021.

  PMID: 1677548 BACKGROUND

• Schmoker JD, Zhuang J, Shackford SR. Hypertonic fluid resuscitation improves cerebral oxygen delivery and reduces intracranial pressure after hemorrhagic shock. J Trauma. 1991 Dec;31(12):1607-13. doi: 10.1097/00005373-199112000-00007.

  PMID: 1749030 BACKGROUND

• Mojtahedzadeh M, Ahmadi A, Mahmoodpoor A, Beigmohammadi MT, Abdollahi M, Khazaeipour Z, Shaki F, Kuochaki B, Hendouei N. Hypertonic saline solution reduces the oxidative stress responses in traumatic brain injury patients. J Res Med Sci. 2014 Sep;19(9):867-74.

  PMID: 25535502 BACKGROUND

• Munar F, Ferrer AM, de Nadal M, Poca MA, Pedraza S, Sahuquillo J, Garnacho A. Cerebral hemodynamic effects of 7.2% hypertonic saline in patients with head injury and raised intracranial pressure. J Neurotrauma. 2000 Jan;17(1):41-51. doi: 10.1089/neu.2000.17.41.

  PMID: 10674757 BACKGROUND

• Rabinovici R, Yue TL, Krausz MM, Sellers TS, Lynch KM, Feuerstein G. Hemodynamic, hematologic and eicosanoid mediated mechanisms in 7.5 percent sodium chloride treatment of uncontrolled hemorrhagic shock. Surg Gynecol Obstet. 1992 Oct;175(4):341-54.

  PMID: 1411892 BACKGROUND

• Wilder DM, Reid TJ, Bakaltcheva IB. Hypertonic resuscitation and blood coagulation: in vitro comparison of several hypertonic solutions for their action on platelets and plasma coagulation. Thromb Res. 2002 Sep 1;107(5):255-61. doi: 10.1016/s0049-3848(02)00335-3.

  PMID: 12479887 BACKGROUND

• Tan TS, Tan KH, Ng HP, Loh MW. The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis: an in vitro assessment using thromboelastography. Anaesthesia. 2002 Jul;57(7):644-8. doi: 10.1046/j.1365-2044.2002.02603.x.

  PMID: 12059821 BACKGROUND

• Reed RL 2nd, Johnston TD, Chen Y, Fischer RP. Hypertonic saline alters plasma clotting times and platelet aggregation. J Trauma. 1991 Jan;31(1):8-14. doi: 10.1097/00005373-199101000-00002.

  PMID: 1986137 BACKGROUND

• Delano MJ, Rizoli SB, Rhind SG, Cuschieri J, Junger W, Baker AJ, Dubick MA, Hoyt DB, Bulger EM. Prehospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsens Hypocoagulation and Hyperfibrinolysis. Shock. 2015 Jul;44(1):25-31. doi: 10.1097/SHK.0000000000000368.

  PMID: 25784523 BACKGROUND

• Ng KF, Lam CC, Chan LC. In vivo effect of haemodilution with saline on coagulation: a randomized controlled trial. Br J Anaesth. 2002 Apr;88(4):475-80. doi: 10.1093/bja/88.4.475.

  PMID: 12066721 BACKGROUND

• Rhind SG, Crnko NT, Baker AJ, Morrison LJ, Shek PN, Scarpelini S, Rizoli SB. Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients. J Neuroinflammation. 2010 Jan 18;7:5. doi: 10.1186/1742-2094-7-5.

  PMID: 20082712 BACKGROUND

• Luostarinen T, Niiya T, Schramko A, Rosenberg P, Niemi T. Comparison of hypertonic saline and mannitol on whole blood coagulation in vitro assessed by thromboelastometry. Neurocrit Care. 2011 Apr;14(2):238-43. doi: 10.1007/s12028-010-9475-6.

  PMID: 21369792 BACKGROUND

• Hanke AA, Maschler S, Schochl H, Floricke F, Gorlinger K, Zanger K, Kienbaum P. In vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch. Scand J Trauma Resusc Emerg Med. 2011 Feb 10;19:12. doi: 10.1186/1757-7241-19-12.

  PMID: 21310047 BACKGROUND

• Gatidis S, Borst O, Foller M, Lang F. Effect of osmotic shock and urea on phosphatidylserine scrambling in thrombocyte cell membranes. Am J Physiol Cell Physiol. 2010 Jul;299(1):C111-8. doi: 10.1152/ajpcell.00477.2009. Epub 2010 Mar 17.

  PMID: 20237147 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, serum

MeSH Terms

Conditions

Intracranial Hypertension; Brain Edema

Interventions

Mannitol; Saline Solution, Hypertonic

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Licia Iacoviello, MD, PhD

  IRCCS Neuromed

  STUDY CHAIR

• Fulvio Aloj, MD

  IRCCS Neuromed

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 24, 2018
• Study Start: December 3, 2020
• Primary Completion: July 1, 2021
• Study Completion: December 31, 2021
• Last Updated: November 19, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)