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

Hemorrhagic Shock Clinical Trial

— HypoResus  

Official title:

Field Trial of Hypotensive Resuscitation Versus Standard Resuscitation in Patients With Hemorrhagic Shock After Trauma: A Pilot Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01411852
• Other study ID #: 41071-B
• Secondary ID: 5U01HL077863-07
• Status: Completed
• Phase: Phase 2
• First received: August 3, 2011
• Last updated: December 30, 2014
• Start date: March 2012
• Est. completion date: April 2013

Study information

• Verified date: December 2014
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Blunt Trauma
• Hemorrhagic Shock
• Penetrating Wound
• Shock
• Shock, Hemorrhagic
• Wounds and Injuries
• Wounds, Penetrating

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Resuscitation Outcomes Consortium Regional Coordinating Center,University of British Columbia	Vancouver	British Columbia
United States	Alabama Resuscitation Center, University of Alabama	Birmingham	Alabama
United States	Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center	Dallas	Texas
United States	Milwaukee Resuscitation Network, Medical College of Wisconsin	Milwaukee	Wisconsin
United States	The Pittsburgh Resuscitation Network, University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
University of Washington	Canadian Institutes of Health Research (CIHR), National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Volume of All Crystalloid Given for Early Resuscitation (Feasibility)	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	From time of first intravenous or intraosseous insertion through the first 2 hours after hospital arrival or hemorrhage control, which ever occurs first
Primary	24 Hour Mortality	The 24 hour mortality endpoint for the total number of patients each arm	From time of hospital arrival through the first 24 hours
Secondary	Number of Ineligible Patients Enrolled at the Time of Randomization	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 5.3 Exclusion Criteria; Excluded will be those with: Ground level falls; Evidence of severe blunt or penetrating head injury with a Glasgow Coma Score (GCS) = 8; Bilateral paralysis secondary to suspected spinal cord injury; Fluid greater than 250 ml was given prior to randomization; Cardiopulmonary resuscitation (CPR) by Emergency Medical Services (EMS) prior to randomization; Known prisoners; Known or suspected pregnancy; Drowning or asphyxia due to hanging; Burns Total Body Surface Area (TBSA) > 20%; Time of call received at dispatch to study intervention > 4 hours	From the time the paramedic with study drug kit arrived at patient's side to the time kit was opened prior to ED arrival
Secondary	Total Fluid Requirement During First 24 Hours	Total volume of fluid administered during the first 24 hours inclusive of crystalloids, blood products, 3% saline, mannitol, and other colloids	From ED arrival through the first 24 hours
Secondary	Total Blood Product Requirements in First 24 Hours	Total amount of blood products required: packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (plts), cryoprecipitate (cryo)	From ED arrival through the first 24 hours
Secondary	Base Deficit on Admission to the Emergency Department (ED)	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.	From final Emergency Department arrival time through first 24 hours
Secondary	Hemoglobin on Admission to the Emergency Department	The first hemoglobin value reported from blood drawn in the final Emergency Department	From final Emergency Department arrival time through first 24 hours
Secondary	Platelet Value on Admission	First platelet value from blood drawn in the the first 24 hours after arrival	From final Emergency Department arrival time through first 24 hours
Secondary	International Normalized Ratio (INR) on Admission to the Emergency Department	The first International normalized ratio (INR) value reported from blood drawn within the first 24 hours from arrival	From final Emergency Department arrival time through first 24 hours
Secondary	Hemorrhage Control Procedure Within 2 Hours of ED Arrival	Hemorrhage control procedures include blood vessel ligated or embolized, organ packed or removed, laparotomy or thoracotomy	From ED arrival through the first 2 hours
Secondary	Acute Renal Failure Classification Score of "Risk" Without Glomerular Filtration Rate (GFR)	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.	From ED arrival through Day 28
Secondary	Acute Renal Failure Classification Score of "Injury" Without Glomerular Filtration Rate (GFR)	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.	From ED arrival through Day 28
Secondary	Acute Renal Failure Classification Score of "Failure" Without Glomerular Filtration Rate (GFR)	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.	From ED arrival through the first 24 hours
Secondary	Ventilator Free Days 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).	From day of the 911 call through Day 28
Secondary	Days Alive Out of the Intensive Care Unit (ICU) 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	From day of the 911 call through Day 28
Secondary	Days Alive Out of the Hospital 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	From day of the 911 call through Day 28
Secondary	Blunt Trauma 24 Hour Mortality	The 24 hour mortality endpoint for the total number of patients injured by blunt mechanisms in each arm.	From time of hospital arrival through first 24 hours
Secondary	Penetrating Trauma 24 Hour Mortality	The 24 hour mortality endpoint for the total number of patients injured by penetrating mechanisms in each arm.	From time of hospital arrival through first 24 hours
Secondary	In-hospital Mortality	Number of patients who died prior to discharge.	From day of the 911 call through hospital discharge

External Links

•   Resuscitation Outcomes Consortium