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Analgesics in the Pre-hospital Setting: Implications on Hemorrhage Tolerance - Ketamine

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ClinicalTrials.gov Identifier: NCT03621085
Recruitment Status : Completed
First Posted : August 8, 2018
Results First Posted : November 26, 2021
Last Update Posted : November 26, 2021
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Craig Crandall, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE August 1, 2018
First Posted Date  ICMJE August 8, 2018
Results First Submitted Date  ICMJE September 16, 2021
Results First Posted Date  ICMJE November 26, 2021
Last Update Posted Date November 26, 2021
Actual Study Start Date  ICMJE June 1, 2018
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2021)
Cumulative Stress Index [ Time Frame: 12 month ]
Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and ketamine limbs, by causing progressive central hypovolemia via lower-body negative pressure (LBNP). This progressive lower-body negative pressure challenge will be performed until the onset of syncopal symptoms (defined as: profound bradycardia, a precipitous drop in arterial blood pressure and accompanying narrowing of pulse pressure, a sustained systolic blood pressure less than 80 mmHg, and/or subjective symptoms such as light-headedness, sweating, nausea, or dizziness). The primary variable will be the quantification of lower-body negative pressure that is required to cause these symptoms. This quantification will be objectively measured via a cumulative stress index which is calculated as the sum of the product of the LBNP level and the duration of each level, until test termination (i.e., 40 mmHg x 3 min + 50 mmHg x 3 min, etc).
Original Primary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
Tolerance to simulated hemorrhage [ Time Frame: 14 month ]
Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and ketamine limbs, by causing progressive central hypovolemia via lower-body negative pressure. This progressive lower-body negative pressure challenge will be performed until the onset of syncopal symptoms (defined as: profound bradycardia, a precipitous drop in arterial blood pressure and accompanying narrowing of pulse pressure, a sustained systolic blood pressure less than 80 mmHg, and/or subjective symptoms such as light-headedness, sweating, nausea, or dizziness). The primary variable will be the quantification of lower-body negative pressure that is required to cause these symptoms. This quantification will be objectively measured via a cumulative stress index which is calculated as the sum of the product of the LBNP level and the duration of each level, until test termination (i.e., 40 mmHg x 3 min + 50 mmHg x 3 min, etc).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2021)
Pressure Pain Tolerance [ Time Frame: 12 months ]
Pain assessments will be conducted using a digital algometer to obtain maximum pain thresholds caused by pressure. This pain assessment technique is conducted by applying the tip of a hand-held digital algometer on the subject's digit. Force is gradually increased and the peak force is recorded when the subject first reports a painful sensation. Removal of the pressure from the algometer immediately relieves the painful sensation and the subject can voluntarily stop the test at any time. This assessment will be performed after the subject has received placebo and ketamine.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
Pain Assessment - Algometer [ Time Frame: 14 months ]
Pain assessments will be conducted using a digital algometer to obtain maximum pain thresholds caused by pressure. This pain assessment technique is conducted by applying the tip of a hand-held digital algometer on the subject's digit. Force is gradually increased and the peak force is recorded when the subject first reports a painful sensation. Removal of the pressure from the algometer immediately relieves the painful sensation and the subject can voluntarily stop the test at any time. This assessment will be performed when the subject has received placebo and ketamine.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Analgesics in the Pre-hospital Setting: Implications on Hemorrhage Tolerance - Ketamine
Official Title  ICMJE Analgesics in the Pre-hospital Setting: Implications on Hemorrhage Tolerance - Ketamine
Brief Summary The purpose of this project is to test how ketamine, an analgesics currently employed in the pre-hospital setting by the US Army, alters the capacity to tolerate a hemorrhagic insult in humans.
Detailed Description

Pain management on the battlefield is critical for the wellbeing of the soldier. Given that a hemorrhagic injury on the battlefield is virtually always associated with pain, it is paramount that the selected pain medication does not disrupt appropriate physiological mechanisms that are beneficial towards the maintenance of blood pressure and vital organ blood flow during that hemorrhagic insult. Current guidelines for the selection of pain medications of a hemorrhaging soldier are based upon limited scientific evidence, with the vast majority of supporting studies being conducted on anesthetized animals. Thus, the interaction between hemorrhagic shock and pain medications commonly employed on the battlefield is yet to be determined in the conscious humans.

With this background, we will test the hypothesis that ketamine will impair the capacity for a conscious human to tolerate a hemorrhagic insult.

The obtained data will provide the necessary scientific evidence in humans to support the Committee on Tactical Combat Casualty Care (CoTCCC) guidelines on the analgesic of choice for moderate to severe injuries where the casualty is in hemorrhagic shock. Notably, such data will identify the analgesic that least compromises a human's ability to tolerate a hemorrhagic insult, ultimately providing critical information to the combat medic on which analgesic should be employed for such an injury.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Hemorrhage
  • Healthy
Intervention  ICMJE
  • Drug: Ketamine Hydrochloride
    A total of 20 mg of Ketamine Hydrochloride will be administered intravenously
  • Other: Placebo
    Subjects will receive placebo
Study Arms  ICMJE
  • Experimental: Ketamine
    Subjects will receive up to 20 mg Ketamine Hydrochloride while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
    Intervention: Drug: Ketamine Hydrochloride
  • Placebo Comparator: Placebo
    Subjects will receive placebo while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 16, 2021)
43
Original Estimated Enrollment  ICMJE
 (submitted: August 6, 2018)
30
Actual Study Completion Date  ICMJE June 30, 2021
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18-45 years of age
  • Healthy
  • Non-obese (body mass index less than 30 kg/m2)
  • Body mass greater than or equal to 65 kg

Exclusion Criteria:

  • Subjects not in the defined age range
  • Subjects who have cardiac, respiratory, neurological and/or metabolic illnesses
  • Any known history of renal or hepatic insufficiency/disease
  • Pregnancy or breast feeding
  • Body mass less than 65 kg
  • Current smokers, as well as individuals who regularly smoked within the past 3 years
  • Positive urine drug screen
  • Currently taking pain modifying medication(s)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03621085
Other Study ID Numbers  ICMJE STU 092017-068
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Craig Crandall, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE United States Department of Defense
Investigators  ICMJE
Principal Investigator: craig G Crandall, Ph.D. University of Texas Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date October 2021

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