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Field Trial of Hypotensive Versus Standard Resuscitation for Hemorrhagic Shock After Trauma (HypoResus)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01411852
First Posted: August 8, 2011
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Susanne May, University of Washington
August 3, 2011
August 8, 2011
October 3, 2014
October 20, 2014
October 12, 2017
March 2012
April 2013   (Final data collection date for primary outcome measure)
  • Total Volume of All Crystalloid Given for Early Resuscitation (Feasibility) [ Time Frame: From time of first intravenous or intraosseous insertion through the first 2 hours after hospital arrival or hemorrhage control, which ever occurs first ]
    The primary feasibility endpoint was early crystalloid volume (ECV) defined as crystalloid infused from Emergency Medical Services (EMS) arrival at the scene until the end of the study period
  • 24 Hour Mortality [ Time Frame: From time of hospital arrival through the first 24 hours ]
    The 24 hour mortality endpoint for the total number of patients each arm
  • Volume of saline given for resuscitation (feasibility) [ Time Frame: From time of first intravenous or intraosseous access through the first 2 hours after arrival in the final Emergency Department or hemorrhage control, which ever occurs first ]
    The total volume of normal saline administered to the patients during the intervention time frame
  • 24-hour survival (safety) [ Time Frame: From 911 call received at dispatch through the first 24 hours ]
    24-hour survival of the patients
Complete list of historical versions of study NCT01411852 on ClinicalTrials.gov Archive Site
  • Number of Ineligible Patients Enrolled at the Time of Randomization [ Time Frame: From the time the paramedic with study drug kit arrived at patient's side to the time kit was opened prior to ED arrival ]

    Eligibility criteria:

    Inclusion Criteria

    Included will be those with:

    1. Blunt or penetrating injury
    2. Age ≥15yrs or weight ≥50kg if age is unknown
    3. Prehospital SBP ≤ 90 mmHg 5.3 Exclusion Criteria

    Excluded will be those with:

    1. Ground level falls
    2. Evidence of severe blunt or penetrating head injury with a Glasgow Coma Score (GCS) ≤ 8
    3. Bilateral paralysis secondary to suspected spinal cord injury
    4. Fluid greater than 250 ml was given prior to randomization
    5. Cardiopulmonary resuscitation (CPR) by Emergency Medical Services (EMS) prior to randomization
    6. Known prisoners
    7. Known or suspected pregnancy
    8. Drowning or asphyxia due to hanging
    9. Burns Total Body Surface Area (TBSA) > 20%
    10. Time of call received at dispatch to study intervention > 4 hours
  • Total Fluid Requirement During First 24 Hours [ Time Frame: From ED arrival through the first 24 hours ]
    Total volume of fluid administered during the first 24 hours inclusive of crystalloids, blood products, 3% saline, mannitol, and other colloids
  • Total Blood Product Requirements in First 24 Hours [ Time Frame: From ED arrival through the first 24 hours ]
    Total amount of blood products required: packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (plts), cryoprecipitate (cryo)
  • Base Deficit on Admission to the Emergency Department (ED) [ Time Frame: From final Emergency Department arrival time through first 24 hours ]
    The first base deficit value reported from arterial blood lab work drawn after arrival in the final Emergency Department. This measure reflects the acid-base balance in the arterial blood. A negative number indicates that the blood is more acid that normal.
  • Hemoglobin on Admission to the Emergency Department [ Time Frame: From final Emergency Department arrival time through first 24 hours ]
    The first hemoglobin value reported from blood drawn in the final Emergency Department
  • Platelet Value on Admission [ Time Frame: From final Emergency Department arrival time through first 24 hours ]
    First platelet value from blood drawn in the the first 24 hours after arrival
  • International Normalized Ratio (INR) on Admission to the Emergency Department [ Time Frame: From final Emergency Department arrival time through first 24 hours ]
    The first International normalized ratio (INR) value reported from blood drawn within the first 24 hours from arrival
  • Hemorrhage Control Procedure Within 2 Hours of ED Arrival [ Time Frame: From ED arrival through the first 2 hours ]
    Hemorrhage control procedures include blood vessel ligated or embolized, organ packed or removed, laparotomy or thoracotomy
  • Acute Renal Failure Classification Score of "Risk" Without Glomerular Filtration Rate (GFR) [ Time Frame: From ED arrival through Day 28 ]
    Increased plasma creatinine > 1.5 x reference measure (ED admission). Urine criteria is based on 6-hour periods for this level of the RIFLE and cannot be assessed since study data are collected for 24-hour periods. This row includes patients who met the "Injury" and "Failure" criteria as well. Only measured for patients with at least 2 days of ICU stay assessed.
  • Acute Renal Failure Classification Score of "Injury" Without Glomerular Filtration Rate (GFR) [ Time Frame: From ED arrival through Day 28 ]
    Increased plasma creatinine > 2 x reference measure (ED admission) or urine output < 0.5 mL/kg/h x 24h. The RIFLE urine criterion for this level actually specifies a 12 hour period of assessment but study data are collected for 24-hr periods. This row includes patients who met the "Failure" criteria as well. Only measured for patients with at least 2 days of ICU stay assessed.
  • Acute Renal Failure Classification Score of "Failure" Without Glomerular Filtration Rate (GFR) [ Time Frame: From ED arrival through the first 24 hours ]
    Increased plasma creatinine > 3 x reference measure (ED admission) or acute plasma creatinine = 350 umol/L or acute rise = 44 umol/L or urine output < 0.3 mL/k/h x 24h. Only measured for patients with at least 2 days of ICU stay assessed.
  • Ventilator Free Days Through Day 28 [ Time Frame: From day of the 911 call through Day 28 ]
    The number of days beginning with the day of the 911 call counted as "Day 0" through Day 28 during which the patient did not require mechanical ventilation. Deaths are assigned the worst score (0).
  • Days Alive Out of the Intensive Care Unit (ICU) Through Day 28 [ Time Frame: From day of the 911 call through Day 28 ]
    The number of days beginning with the day of the 911 call counted as "Day 0" through Day 28 during which the patient is alive and not being cared for in the intensive care unit
  • Days Alive Out of the Hospital Through Day 28 [ Time Frame: From day of the 911 call through Day 28 ]
    The number of days beginning with the day of the 911 call counted as "Day 0" through Day 28 during which the patient is alive and not being cared for in the hospital
  • Blunt Trauma 24 Hour Mortality [ Time Frame: From time of hospital arrival through first 24 hours ]
    The 24 hour mortality endpoint for the total number of patients injured by blunt mechanisms in each arm.
  • Penetrating Trauma 24 Hour Mortality [ Time Frame: From time of hospital arrival through first 24 hours ]
    The 24 hour mortality endpoint for the total number of patients injured by penetrating mechanisms in each arm.
  • In-hospital Mortality [ Time Frame: From day of the 911 call through hospital discharge ]
    Number of patients who died prior to discharge.
  • Protocol Violations [ Time Frame: From the time of randomization through the first 24 hours following the time the 911 call was received at dispatch ]
    Protocol violations will be assessed in the following measurements: 1. amount of non-missing vital signs (either systolic blood pressure or palpable radial pulse) prior and after administration of each bolus of fluid; 2. consistency between vital signs measure and (non-) continuation of fluid as mandated by the treatment arm; 3. percent of exclusions due to potential head injury
  • Total fluid requirement during intervention period [ Time Frame: From time of first intravenous or intraosseous access through the first 2 hours after arrival in the final Emergency Department or hemorrhage control, whichever occurs first ]
    Total volume of fluid administered during the intervention time frame inclusive of crystalloids, blood products, 3% saline, mannitol, and other colloids
  • Total Fluid Requirement During First 24 Hours [ Time Frame: From 911 call received at dispatch through the first 24 hours ]
    Total volume of fluid administered during the first 24 hours inclusive of crystalloids, blood products, 3% saline, mannitol, and other colloids
  • Total Blood Product Requirements in First 24 Hours [ Time Frame: From 911 call received at dispatch through the first 24 hours ]
    Total amount of blood products required: packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (plts), cryoprecipitate (cryo)
  • Base Deficit on Admission to the Emergency Department (ED) [ Time Frame: From final Emergency Department arrival time through the following 24 hours ]
    The first base deficit value reported from arterial blood lab work drawn after arrival in the final Emergency Department. This measure reflects the acid-base balance in the arterial blood. A negative number indicates that the blood is more acid that normal.
  • Hematocrit and hemaglobin on admission to the Emergency Department [ Time Frame: From final Emergency Department arrival time through the following 24 hours ]
    The first hematocrit and hemaglobin values reported from blood drawn in the final Emergency Department
  • Coagulation Parameters on Admission to the Emergency Department [ Time Frame: From final Emergency Department arrival time through the following 24 hours ]
    The first platelet, protime, prothrombin time, International normalised ratio (INR), and fibrinogen values reported from blood drawn in the final Emergency Department
  • Ventilator Free Days Through Day 28 [ Time Frame: From day of the 911 call through Day 28 ]
    The number of days beginning with the day of the 911 call counted as "Day 0" through Day 28 during which the patient did not require mechanical ventilation. Deaths are assigned the worst score (0).
  • Days Alive Out of the Intensive Care Unit (ICU) Through Day 28 [ Time Frame: From day of the 911 call through Day 28 ]
    The number of days beginning with the day of the 911 call counted as "Day 0" through Day 28 during which the patient is alive and not being cared for in the intensive care unit
  • Days Alive Out of the Hospital Through Day 28 [ Time Frame: From day of the 911 call through Day 28 ]
    The number of days beginning with the day of the 911 call counted as "Day 0" through Day 28 during which the patient is alive and not being cared for in the hospital
  • Worst Acute Renal Failure Classification Score Without Glomerular Filtration Rate (GFR) [ Time Frame: From day of the 911 call through Day 28 ]
    Beginning with the day of the 911 call counted as "Day 0" through Day 28, the worst acute renal failure classification score recorded using the Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) criteria excluding glomerular filtration rate (GFR) calculated using plasma creatinine and urine output based on weight in kilograms. Classifications: 1. Risk; 2. Injury: and 3. Failure
Not Provided
Not Provided
 
Field Trial of Hypotensive Versus Standard Resuscitation for Hemorrhagic Shock After Trauma
Field Trial of Hypotensive Resuscitation Versus Standard Resuscitation in Patients With Hemorrhagic Shock After Trauma: A Pilot Trial

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.

  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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Care Provider)
Primary Purpose: Treatment
  • Blunt Trauma
  • Penetrating Wound
  • Hemorrhagic Shock
  • Drug: 0.9% Sodium Chloride 250 mL bolus
    Emergency Medicine Systems (EMS) agencies and in-hospital providers will be given the option to utilize either systolic blood pressure (SBP) or radial pulse as the endpoint for fluid resuscitation to patients randomized to the experimental group. Patients will receive a 250 ml bolus of normal saline (NS) only if the SBP is less than 70 mmHg or the radial pulse is not palpable. If the SBP is greater than or equal to 70 mmHg or the radial pulse is palpable, NS will be given to keep the vein open. The presence or absence of a radial pulse or the SBP will be documented before and after each bolus. The study will continue repeating the randomization procedure using only 250 ml bags of NS until 2 hours after arrival to the hospital or until hemorrhage control is achieved whichever occurs first.
    Other Names:
    • isotonic saline
    • normal saline
  • Drug: 0.9% Sodium Chloride 2000 mL bolus
    Emergency Medicine Systems (EMS) personnel and in-hospital providers will utilize the systolic blood pressure SBP as the endpoint for delivering fluid resuscitation to patients randomized to the control group. If the SBP is equal to or less than 90 mmHg, the EMS personnel will start infusing a 1000 ml bolus of normal saline (NS) and will continue using only 1000 ml bags of NS as needed. If the total fluid resuscitation exceeds 2 liters, fluid will be stopped when the SBP exceeds 110 mmHg and restarted as necessary to maintain a goal SBP of 110 mmHg. The fluid will be given as rapidly as possible. This fluid resuscitation protocol will continue until either 2 hours after hospital arrival or until control of hemorrhage is achieved whichever occurs first.
    Other Names:
    • isotonic saline
    • normal saline
  • Experimental: 0.9% Sodium Chloride 250 mL bolus
    0.9% Sodium Chloride 250 mL bolus - A large bore IV will be placed and a 250cc bag of normal saline (NS) will be hung. If IV placement is difficult, NS can be given through an intraosseous line. Using small bags versus large bags will physically limit the amount of fluid given to patients in the experimental group. The requirement to change the smaller bags of fluid and recheck the pulse or blood pressure will limit the amount of fluid given. The procedure will continue until 2 hours after arrival to the hospital or until hemorrhage control is achieved whichever occurs first. Hemorrhage control will be defined as ligation of a bleeding vessel, packing of a solid organ, removal of a solid organ, and angiographic embolization of a bleeding vessel.
    Intervention: Drug: 0.9% Sodium Chloride 250 mL bolus
  • Active Comparator: 0.9% Sodium Chloride 2000 mL bolus
    0.9% Sodium Chloride 2000 mL bolus - The treatment of the control group will be consistent with traditional Prehospital Trauma Life Support and Advanced Trauma Life Support guidelines which recommend early aggressive fluid resuscitation. An intravenous line (IV) will be placed and a 1000cc bag of normal saline will be hung. If IV placement is difficult, fluid can be given through an intraosseous line. This procedure will continue until either 2 hours after hospital arrival or until control of hemorrhage is achieved whichever occurs first. Hemorrhage control will be defined as ligation of a bleeding vessel, packing of a solid organ, removal of a solid organ, and angiographic embolization of a bleeding vessel.
    Intervention: Drug: 0.9% Sodium Chloride 2000 mL bolus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
192
April 2013
April 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
15 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
 
 
NCT01411852
41071-B
5U01HL077863-07 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Susanne May, University of Washington
University of Washington
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Canadian Institutes of Health Research (CIHR)
Study Chair: Myron L Weisfeldt, MD Resuscitation Outcomes Consortium
Study Director: David Hoyt, MD Resuscitation Outcomes Consortium
University of Washington
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP