Hypertonic Resuscitation Following Traumatic Injury

This study has been terminated.
(Futility & potential safety concern (increased early mortality in the HS/HSD arms for those with no PRBC in 1st 24 hr, post-randomization subgp))
Sponsor:
Collaborators:
The Institute of Circulatory and Respiratory Health (ICRH)
Defence Research and Development Canada
Information provided by:
University of Washington
ClinicalTrials.gov Identifier:
NCT00316017
First received: April 17, 2006
Last updated: February 25, 2011
Last verified: February 2011
Results First Received: September 2, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Shock, Traumatic
Interventions: Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)
Drug: 7.5% hypertonic saline (HS)
Drug: 0.9% normal saline

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled by Emergency Medicine Services (EMS) personnel in the pre-hospital setting based on pre-defined inclusion/exclusion criteria. The first subject was enrolled on May 9, 2006 and the last subject was enrolled on August 25, 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
895 subjects were randomized. 852 subjects completed the study. Randomization was performed when the outer study fluid bag wrapper was removed in the presence of a patient. To ensure there was no bias, a secondary intention to treat analysis was also performed which included all randomized patients even if the fluid was not administered.

Reporting Groups
  Description
7.5% Hypertonic Saline/6% Dextran-70 (HSD) 7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
7.5% Hypertonic Saline (HS) 7.5% hypertonic saline (HS) 250ml dose
0.9% Normal Saline 0.9% normal saline 250 ml dose as placebo

Participant Flow:   Overall Study
    7.5% Hypertonic Saline/6% Dextran-70 (HSD)     7.5% Hypertonic Saline (HS)     0.9% Normal Saline  
STARTED     231 [1]   269 [2]   395 [3]
COMPLETED     220     256     376  
NOT COMPLETED     11     13     19  
Protocol Violation                 11                 13                 19  
[1] 11 of 11 not completed due to "Bag Opened Not Given" (BONG)
[2] 12 of 13 not completed due to BONG; 1 not completed was a prisoner who was excluded
[3] 19 of 19 not complete due to BONG



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
7.5% Hypertonic Saline/6% Dextran-70 (HSD) 7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
7.5% Hypertonic Saline (HS) 7.5% hypertonic saline (HS) 250ml dose
0.9% Normal Saline 0.9% normal saline 250 ml dose as placebo
Total Total of all reporting groups

Baseline Measures
    7.5% Hypertonic Saline/6% Dextran-70 (HSD)     7.5% Hypertonic Saline (HS)     0.9% Normal Saline     Total  
Number of Participants  
[units: participants]
  220     256     376     852  
Age [1]
[units: participants]
       
<=18 years     13     13     23     49  
Between 18 and 65 years     188     225     332     745  
>=65 years     18     18     21     57  
Age [1]
[units: years]
Mean ± Standard Deviation
  37.7  ± 17.3     36.8  ± 16.1     36.2  ± 16.4     36.7  ± 16.5  
Gender [2]
[units: participants]
       
Female     50     51     85     186  
Male     170     205     291     666  
Region of Enrollment  
[units: participants]
       
United States     177     212     283     672  
Canada     43     44     93     180  
[1] The HSD group included one subject with no age data available.
[2] Description only includes those subjects who received the study fluid.



  Outcome Measures
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1.  Primary:   28 Day Survival   [ Time Frame: 28 days from time of Emergency Department (ED) arrival ]

2.  Secondary:   Adult Respiratory Distress Syndrome(ARDS)-Free Survival Through Day 28   [ Time Frame: 28 days from time of ED arrival ]

3.  Secondary:   Worst Multiple Organ Dysfunction Score (MODS) Mean Through Day 28   [ Time Frame: 28 days from time of ED arrival ]

4.  Secondary:   Presence of Nosocomial Infection Through Day 28   [ Time Frame: Within 28 days of injury, while hospitalized ]

5.  Secondary:   Packed Red Blood Cells (PRBC) First 24 Hours   [ Time Frame: First 24 hours from the time of 911 call ]

6.  Secondary:   Total Fluids First 24 Hours   [ Time Frame: First 24 hours from the time of of 911 call ]

7.  Secondary:   Ventilator-free Days Through Day 28   [ Time Frame: Duration of hospital stay through day 28 ]

8.  Secondary:   Days Alive Out of the Intensive Care Unit (ICU) Through Day 28   [ Time Frame: First 28 days from the time of 911 call ]

9.  Secondary:   Days Alive Out of the Hospital Through Day 28   [ Time Frame: First 28 days from the time of 911 call ]

10.  Secondary:   Survival at Hospital Discharge   [ Time Frame: Duration of hospital stay through to discharge ]

11.  Secondary:   Zero Units PRBC in First 24 Hours   [ Time Frame: From the time dispatch received the 911 call to the end of the first 24 hours ]

12.  Secondary:   Zero Units PRBC and Died in Field or Emergency Department (ED)   [ Time Frame: From the time dispatch received 911 call to the time of death in the field or ED ]

13.  Secondary:   Zero Units PRBC and Died Within 6 Hours of Admission to the Hospital   [ Time Frame: The first 6 hours from the time of admission to the hospital ]

14.  Secondary:   Zero Units PRBC and Died Within 28 Days From the Time of the 911 Call   [ Time Frame: From the time dispatch received the 911 call to 28 days ]

15.  Secondary:   1-9 Units PRBC in First 24 Hours   [ Time Frame: From the time dispatch received the 911 call to the end of the first 24 hours ]

16.  Secondary:   1-9 Units PRBC and Died in Field or ED   [ Time Frame: From the time dispatch received 911 call to the time of death in the field or ED ]

17.  Secondary:   1-9 Units PRBC and Died Within 6 Hours of Admission to the Hospital   [ Time Frame: The first 6 hours from the time of admission to the hospital ]

18.  Secondary:   1-9 Units PRBC and Died Within 28 Days From the Time of the 911 Call   [ Time Frame: From the time dispatch received the 911 call to 28 days ]

19.  Secondary:   Greater Than 10 Units PRBC in First 24 Hours   [ Time Frame: From the time dispatch received the 911 call to the end of the first 24 hours ]

20.  Secondary:   Greater Than 10 Units PRBC and Died in Field or ED   [ Time Frame: From the time dispatch received 911 call to the time of death in the field or ED ]

21.  Secondary:   Greater Than 10 Units PRBC and Died Within 6 Hours of Admission to the Hospital   [ Time Frame: The first 6 hours from the time of admission to the hospital ]

22.  Secondary:   Greater Than 10 Units PRBC and Died Within 28 Days From the Time of the 911 Call   [ Time Frame: From the time dispatch received the 911 call to 28 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The trial was stopped early for futility in the presence of a potential safety concern regarding increased mortality among patients receiving hypertonic solutions and no blood transfusions. This was no longer evident 6 hr after hospital admission.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Susanne May, PhD
Organization: Clinical Trial Center, University of Washington, Seattle, WA
phone: 206-685-1302
e-mail: sjmay@uw.edu


Publications of Results:

Responsible Party: Gerald van Belle, PhD/Prinicipal Investigator, Resuscitation Outcomes Consortium Data Coordinating Center
ClinicalTrials.gov Identifier: NCT00316017     History of Changes
Other Study ID Numbers: 28226-A - IND 12506, 5U01HL077863-05, IND #12506 (shock cohort)
Study First Received: April 17, 2006
Results First Received: September 2, 2010
Last Updated: February 25, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada
Canada: Ethics Review Committee