Hypertonic Modulation of Inflammation Following Injury

Traumatic Brain Injury Clinical Trial

Official title:

Hypertonic Modulation of Inflammation Following Injury

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00750997
• Other study ID #: 28233
• Status: Terminated
• Phase: N/A
• First received: September 10, 2008
• Last updated: April 27, 2017
• Start date: November 2007
• Est. completion date: December 2009

Study information

• Verified date: April 2017
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This project seeks to determine the effect of prehospital resuscitation with hypertonic saline vs. conventional crystalloids on the inflammatory response after injury. The leading cause of late mortality following injury is multiple organ dysfunction syndrome (MODS), which results from a dysfunctional inflammatory response after injury. Previous studies suggest that hypertonic saline may be beneficial by modulating this initial response and decreasing subsequent organ injury. This project takes advantage of a unique opportunity, afforded by an NIH-funded multi-center clinical trial of hypertonic resuscitation (conducted by the Resuscitation Outcomes Consortium), to obtain blood samples from patients enrolled in this trial to analyze inflammatory responses early after hypertonic vs. conventional resuscitation. This study was an ancillary study to the main randomized clinical trial and thus prospective observational in nature

The proposed study will be carried out in experiments grouped in three Specific Aims: Aim 1 provides a thorough investigation of the immunomodulatory response following hypertonic resuscitation with regard to neutrophil, monocyte, and T cell responses at serial time points after injury and resuscitation. Aim 2 comprises experiments to investigate the mechanisms by which hypertonicity may alter inflammatory cell signaling. Aim 3 seeks to correlate the laboratory findings with clinical endpoints reflective of immune dysfunction including inflammation, organ failure, nosocomial infection, and sepsis.

The investigators hypothesize that hypertonic resuscitation will be associated with modulation of the excessive inflammatory response seen after injury and thus will result in reduced rates of inflammatory organ injury.

Description:

This was an ancillary study to the larger clinical trials of prehospital hypertonic resuscitation conducted by the resuscitation outcomes consortium. This study investigated markers of immune function and coagulation in a subset of patients enrolled in the larger trials at two of the clinical sites. Four publications detail the results please see references

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 119
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Blunt or Penetrating trauma with prehospital systolic blood pressure < 70 or 70-90 mmHg with Heart rate > 108 OR Blunt trauma with prehospital Glasgow coma score <= 8

Exclusion Criteria:

• Age < 15 yrs

• Known prisoners

• Pregnancy

• Ongoing Cardiopulmonary resuscitation (CPR)

• Burns < 20%

• Hypothermia < 28 C

• > 2 liters intravenous fluid prior to study fluid administration

• > 4 hour from time of dispatch

Related Conditions & MeSH terms

• Brain Injuries
• Hemorrhagic Shock
• Inflammation
• Shock, Hemorrhagic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• hypertonic saline
patients in parent trial were randomized to 250cc 7.5% saline, 7.5%saline with 6%dextran or normal saline as control as the initial resuscitation fluid after injury with signs of either hemorrhagic shock or severe traumatic brain injury

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

Bulger EM, Tower CM, Warner KJ, Garland T, Cuschieri J, Rizoli S, Rhind S, Junger WG. Increased neutrophil adenosine a3 receptor expression is associated with hemorrhagic shock and injury severity in trauma patients. Shock. 2011 Nov;36(5):435-9. doi: 10.1 — View Citation

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. — View Citation

Junger WG, Rhind SG, Rizoli SB, Cuschieri J, Baker AJ, Shek PN, Hoyt DB, Bulger EM. Prehospital hypertonic saline resuscitation attenuates the activation and promotes apoptosis of neutrophils in patients with severe traumatic brain injury. Shock. 2013 Nov — View Citation

Junger WG, Rhind SG, Rizoli SB, Cuschieri J, Shiu MY, Baker AJ, Li L, Shek PN, Hoyt DB, Bulger EM. Resuscitation of traumatic hemorrhagic shock patients with hypertonic saline-without dextran-inhibits neutrophil and endothelial cell activation. Shock. 201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	neutrophil activation	several parameters of neutrophil activation were assessed	Emergency department admission
Secondary	Endothelial cell activation	several parameters of endothelial cell activation were assessed	Emergency department admission
Secondary	coagulation parameters	several parameters of coagulation were assessed	Emergency department admission
Secondary	monocyte activation	several parameters of monocyte activation were assessed	Emergency department admission

External Links

•   Website for Resuscitation Outcomes Consortium