Hemorrhagic ShockNCT00750997
Hypertonic Modulation of Inflammation Following Injury
An observational study of Hemorrhagic Shock and Traumatic Brain Injury, run by University of Washington at 2 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Hemorrhagic Shock, Traumatic Brain Injury
- What is being tested?
- hypertonic saline
- How many people
- 119 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Nov 2007to Dec 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients enrolled in clinical trial of Hypertonic Resuscitation based on prehospital evidence of hypovolemic shock or severe brain injury
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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.
Read the detailed 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
- Conditions
- Hemorrhagic Shock, Traumatic Brain Injury
- Being tested
- hypertonic saline
- Medical subject headings
- Shock, Hemorrhagic, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypertonic salineDrug
Also called hypertonic saline with dextran
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
| Study group | Role | What they receive |
|---|---|---|
| Hypertonic saline | Hypertonic resuscitation Receives: Drug: hypertonic saline | |
| Control: normal saline | Normal saline resuscitation |
What is being measured
The primary outcome is the main question the study is designed to answer.
neutrophil activation
several parameters of neutrophil activation were assessed
Measured: Emergency department admission
Secondary outcomes (3)
Endothelial cell activation
several parameters of endothelial cell activation were assessed
Measured: Emergency department admission
coagulation parameters
several parameters of coagulation were assessed
Measured: Emergency department admission
monocyte activation
several parameters of monocyte activation were assessed
Measured: Emergency department admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2008 (estimated)
- Study startNov 2007
- Primary completionDec 2009
- Study completionDec 2009
Why it stopped: Enrollment in the clinical trial was stopped for futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hemorrhagic ShockStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eileen Bulger, University of Washington
- Investigators
- Eileen M Bulger, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00750997
- Sponsor's protocol ID
- 28233
- Status last verified
- Apr 2017
- First submitted
- 10 Sep 2008
- Last updated
- 1 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Data from the primary RCT will be made available through the Resuscitation Outcomes consortium. This was an ancillary study
Publications
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.
PubMed 25784523Junger 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;40(5):366-74. doi: 10.1097/SHK.0000000000000038.
PubMed 24088993Junger 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. 2012 Oct;38(4):341-50. doi: 10.1097/SHK.0b013e3182635aca.
PubMed 22777113Bulger 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: 10.1097/SHK.0b013e318231ee2e.
PubMed 21841534
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypertonic Modulation of Inflammation Following Injury
- ClinicalTrials.gov ID
- NCT00750997
- Acronym / sponsor ID
- 28233
- Conditions
- Hemorrhagic Shock, Traumatic Brain Injury
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Enrollment in the clinical trial was stopped for futility
- Enrolment
- 119 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 11 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypertonic saline | – | Drug: hypertonic salineHypertonic resuscitation |
| Control: normal saline | – | –Normal saline resuscitation |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients enrolled in clinical trial of Hypertonic Resuscitation based on prehospital evidence of hypovolemic shock or severe brain injury
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (8 listed)
- Age < 15 yrs
- Known prisoners
- Pregnancy
- Ongoing Cardiopulmonary resuscitation (CPR)
- Burns < 20%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hypertonic salineAlso: hypertonic saline with dextranpatients 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 | Drug | Hypertonic saline |
Primary outcome
neutrophil activation
Time frame: Emergency department admission
several parameters of neutrophil activation were assessed
3 secondary outcomes
Endothelial cell activation
Time frame: Emergency department admission
coagulation parameters
Time frame: Emergency department admission
monocyte activation
Time frame: Emergency department admission
Results and safety
The study was stopped early (reason given: Enrollment in the clinical trial was stopped for futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2017.
- Results publication: PubMed 25784523Delano 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.
- Results publication: PubMed 24088993Junger 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;40(5):366-74. doi: 10.1097/SHK.0000000000000038.
- Results publication: PubMed 22777113Junger 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. 2012 Oct;38(4):341-50. doi: 10.1097/SHK.0b013e3182635aca.
- Results publication: PubMed 21841534Bulger 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: 10.1097/SHK.0b013e318231ee2e.
- Individual participant dataSharing planned: No. Data from the primary RCT will be made available through the Resuscitation Outcomes consortium. This was an ancillary study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eileen M Bulger, MD principal investigator
University of Washington
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemorrhagic Shock and Traumatic Brain Injury, run by University of Washington at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Enrollment in the clinical trial was stopped for futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
neutrophil activation (time frame: Emergency department admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00750997, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2017.