Clinical trial NCT01411852: Field Trial of Hypotensive Versus Standard Resuscitation for Hemorrhagic Shock After Trauma
Official title: Field Trial of Hypotensive Resuscitation Versus Standard Resuscitation in Patients With Hemorrhagic Shock After Trauma: A Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Blunt Trauma
Penetrating Wound
Hemorrhagic Shock
Keywords: fluid volume resuscitation
trauma
hemorrhagic shock
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Canadian Institutes of Health Research (CIHR)
First posted: 2011-08-08
Enrollment: 192
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Aim: To determine the feasibility and safety of hypotensive resuscitation for the early treatment of patients with traumatic shock compared to standard fluid resuscitation.

Primary Hypotheses: The null hypothesis regarding feasibility is that hypotensive resuscitation will result in the same volume of early crystalloid (normal saline) fluid administration compared to standard crystalloid resuscitation. The null hypothesis regarding safety is that hypotensive resuscitation will result in the same percent of patients surviving to 24 hours after 911 call received at dispatch compared to standard fluid resuscitation. Early resuscitation is defined as all fluid given until 2 hours after arrival in the Emergency Department or until hemorrhage control is achieved in the hospital, whichever occurs earlier.

Detailed description: 1. Overview This multi-center pilot trial is designed to determine the feasibility and safety of hypotensive resuscitation for the early resuscitation of patients with traumatic shock compared to standard fluid resuscitation. Blunt and penetrating trauma patients with a prehospital systolic blood pressure (SBP) ≤ 90 mmHg will be eligible. In the hypotensive resuscitation group, an intravenous line (IV) will be placed and a radial pulse will be palpated. If the radial pulse is present or the SBP is greater than or equal to 70, a 250 ml bag of normal saline will be hung and maintained at a keep the vein open rate only. If the radial pulse is absent, the 250 ml of normal saline will be given as a bolus. This process using small bags of fluid will be repeated until a radial pulse is palpable or until 2 hours after Emergency Department (ED) arrival or until hemorrhage control has been achieved. The decision to utilize a SBP versus a radial pulse will be made a priori. Patients in the standard fluid resuscitation group will have an IV placed and a 1000 ml bag of normal saline (NS) will be hung. Fluid will be given as rapidly as possible and continued until hospital arrival. If the prehospital or hospital fluid resuscitation exceeds 2 liters, it will be stopped when the SBP exceeds 110 mmHg and restarted as necessary to maintain a goal SBP of 110 mmHg. This randomization scheme will be continued for 2 hours after hospital arrival or until hemorrhage control is achieved whichever occurs first. The randomization will not affect the indications for the administration of blood products but we hypothesize that less blood products and total fluid will be given in the experimental group due to avoidance of the pop-the-clot phenomenon, less hemodilution and less coagulopathy.

   Patients who experience ground level falls are characterized as having low injury severity scores. (70) Patients with suspected ground level falls will be excluded in an effort to focus enrollment on the more severely injured patients at risk for trauma related hemorrhagic shock. Patients with severe traumatic brain injury will be excluded due to lack of equipoise. In observational studies (1-5) a relationship between hypotension and poor neurologic outcomes has been observed and EMS personnel as well as researchers at this time believe that it is unethical to withhold resuscitation fluid from patients with traumatic brain injury. Patients with suspected spinal cord injury will also be excluded based on evidence that indicates they are at risk for cardiovascular failure due to hemodynamic compromise correlated with the presence of neurogenic hypotension at the time of hospital admission. (69) All enrolled patients will be retrospectively screened to determine if they had evidence of severe traumatic brain injury with GCS≤8 or spinal cord injury at the time of enrollment.

   Screening information will be obtained for all potentially eligible patients who meet all inclusion criteria. Screening will also document whether each exclusion criterion is met. The rate at which screened patients were enrolled and later found to have met one or more of the exclusion criteria will be assessed to determine if the inclusion and exclusion criteria need to be adjusted to avoid enrollment of these patients for future studies. These patients will also be assessed to determine if enrollment in the protocol potentially harmed these patients.

   The study will be a two arm, randomized interventional trial comparing the two resuscitation strategies. Due to obvious differences in the treatment of enrolled patients, the study will not be blinded. Nevertheless, treatment bags will be packaged in containers such that providers will not be able to identify whether treatment containers house 1000 ml bags or 250 ml bags until the treatment containers are opened. The patient will be considered randomized at the time a study bag is opened regardless of whether any fluid is given or not. Hospitals will be provided with 250 ml bags of NS to continue treatment of those patients randomized to the hypotensive resuscitation arm.

   The primary outcomes of the study will be volume of prehospital and in-hospital fluid administered from time of injury until 2 hours into the hospital stay or until hemorrhage is controlled to test feasibility and 24 hour survival for the safety hypothesis. Secondary outcomes will include measures of protocol adherence, 24 hour fluid volume, 24 hour blood product requirements, ventilator days, hospital length of stay, intensive care unit (ICU) length of stay, admission base deficit, development of renal failure, admission hematocrit and admission coagulation parameters. The primary goals of this pilot study will be to determine if the described model will result in different early fluid volumes being delivered to the two groups and to determine if these differing volumes impact mortality. If this pilot study shows that hypotensive resuscitation is feasible and safe, a larger trial will be planned to determine the efficacy of hypotensive fluid resuscitation.

   This study will be conducted by the Resuscitation Outcomes Consortium (ROC) which is a collaboration of 7 regional sites in the United States and Canada and a Data Coordinating Center. This consortium is charged with the task of conducting clinical trials in patients with life threatening trauma and cardiac arrest. The following ROC sites have committed to participating in this trial: Alabama, Dallas, Milwaukee, Ottawa, Pittsburgh, Portland, and Vancouver.
2. Specific Aims and Hypotheses Specific Aim 1: To investigate whether early crystalloid (normal saline) resuscitation volume can be reduced for trauma patients with hemorrhagic shock who receive hypotensive resuscitation versus those who receive standard early resuscitation (feasibility) and whether there are differences in 24-hour survival between the groups (safety).

Primary Hypotheses: The null hypothesis is that patients who receive hypotensive resuscitation and patients who receive standard resuscitation will have the same volume of early crystalloid (normal saline) resuscitation administered and will have the same 24-hour survival from 911 call received at dispatch time.

Specific Aim 2: To assess protocol adherence and differences in morbidity and adverse events for hypotensive versus standard resuscitation.

Secondary Hypotheses: The null hypotheses are that protocol adherence is low and that hypotensive resuscitation versus standard resuscitation will result in the same amount of total fluid volume and total blood product requirements within 24 hours from 911 call received at dispatch, the same base deficit, hematocrit and coagulation parameters on admission to the ED, number of days on a ventilator, duration of hospital stay, ICU length of stay, and incidence of renal failure.

Eligibility criteria: Inclusion Criteria: Included will be those with:

* Blunt or penetrating injury
* Age ≥15yrs or weight ≥50kg if age is unknown
* Prehospital SBP ≤ 90 mmHg

Exclusion Criteria: Excluded will be those with:

* Ground level falls
* Evidence of severe blunt or penetrating head injury with a Glasgow Coma Scale (GCS) ≤ 8
* Bilateral paralysis secondary to suspected spinal cord injury
* Fluid greater than 250ml was given prior to randomization
* Cardiopulmonary resuscitation (CPR) by Emergency Medicine Service (EMS) prior to randomization
* Known prisoners
* Known or suspected pregnancy
* Drowning or asphyxia due to hanging
* Burns over a Total Body Surface Area (TBSA) \> 20%
* Time of call received at dispatch to study intervention \> 4 hours

Primary outcomes:
measure: Total Volume of All Crystalloid Given for Early Resuscitation (Feasibility)
timeFrame: From time of first intravenous or intraosseous insertion through the first 2 hours after hospital arrival or hemorrhage control, which ever occurs first
measure: 24 Hour Mortality
timeFrame: From time of hospital arrival through the first 24 hours
Secondary outcomes:
measure: Number of Ineligible Patients Enrolled at the Time of Randomization
timeFrame: From the time the paramedic with study drug kit arrived at patient's side to the time kit was opened prior to ED arrival
measure: Total Fluid Requirement During First 24 Hours
timeFrame: From ED arrival through the first 24 hours
measure: Total Blood Product Requirements in First 24 Hours
timeFrame: From ED arrival through the first 24 hours
measure: Base Deficit on Admission to the Emergency Department (ED)
timeFrame: From final Emergency Department arrival time through first 24 hours
measure: Hemoglobin on Admission to the Emergency Department
timeFrame: From final Emergency Department arrival time through first 24 hours
measure: Platelet Value on Admission
timeFrame: From final Emergency Department arrival time through first 24 hours
measure: International Normalized Ratio (INR) on Admission to the Emergency Department
timeFrame: From final Emergency Department arrival time through first 24 hours
measure: Hemorrhage Control Procedure Within 2 Hours of ED Arrival
timeFrame: From ED arrival through the first 2 hours
measure: Acute Renal Failure Classification Score of "Risk" Without Glomerular Filtration Rate (GFR)
timeFrame: From ED arrival through Day 28
measure: Acute Renal Failure Classification Score of "Injury" Without Glomerular Filtration Rate (GFR)
timeFrame: From ED arrival through Day 28
measure: Acute Renal Failure Classification Score of "Failure" Without Glomerular Filtration Rate (GFR)
timeFrame: From ED arrival through the first 24 hours
measure: Ventilator Free Days Through Day 28
timeFrame: From day of the 911 call through Day 28
measure: Days Alive Out of the Intensive Care Unit (ICU) Through Day 28
timeFrame: From day of the 911 call through Day 28
measure: Days Alive Out of the Hospital Through Day 28
timeFrame: From day of the 911 call through Day 28
measure: Blunt Trauma 24 Hour Mortality
timeFrame: From time of hospital arrival through first 24 hours
measure: Penetrating Trauma 24 Hour Mortality
timeFrame: From time of hospital arrival through first 24 hours
measure: In-hospital Mortality
timeFrame: From day of the 911 call through hospital discharge
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Resuscitation Center, University of Alabama
state: Alabama
city: Portland
country: United States
facility: Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: The Pittsburgh Resuscitation Network, University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center
state: Texas
city: Milwaukee
country: United States
facility: Milwaukee Resuscitation Network, Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: Resuscitation Outcomes Consortium Regional Coordinating Center,University of British Columbia
state: British Columbia
Study officials:
affiliation: Resuscitation Outcomes Consortium
name: Myron L Weisfeldt, MD
role: STUDY_CHAIR
affiliation: Resuscitation Outcomes Consortium
name: David Hoyt, MD
role: STUDY_DIRECTOR
References: