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

This study will examine how sufentanil (a commonly used pain medication) will alter responses to simulated blood loss in humans. To simulate blood loss in the research laboratory, participants will complete a test with their lower body in a custom-designed vacuum chamber for a brief period of time.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Sufentanil; Other: Placebo

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.

This study will test the hypothesis that sufentanil 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: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75231
      • Institute for Exercise and Environmental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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
• Speak English

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
• Subjects who cannot speak or read English
• Positive urine drug screen
• Currently taking pain modifying medication(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sufentanil; Sufentanil (30 microgram tablet) will be administered via a sublingual pill	Drug: Sufentanil; Subjects will receive Sufentanil while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Placebo Comparator: Placebo; Placebo will be administered via a sublingual pill	Other: Placebo; Subjects will receive a placebo pill while the effects of this placebo on tolerance to a hemorrhagic insult will be assessed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance to simulated hemorrhage	Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and sufentanil limbs, by causing progressive central hypovolemia via lower-body negative pressure. This progressive lower-body negative pressure (LBNP) 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).	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Assessment	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 sufentanil.	18 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: June 29, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Sufentanil
• Other Study ID Numbers: STU-2021-0579

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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.: Yes