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

• ClinicalTrials.gov Identifier: NCT04138615
• Recruitment Status: Completed
• First Posted: October 24, 2019
• Results First Posted: January 12, 2023
• Last Update Posted: January 12, 2023
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Craig Crandall, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Morphine; Other: Placebo	Phase 1; Phase 2

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 morphine 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Analgesics in the Pre-hospital Setting: Implications on Hemorrhage Tolerance - Morphine
• Actual Study Start Date: November 12, 2019
• Actual Primary Completion Date: January 4, 2022
• Actual Study Completion Date: January 4, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Morphine; Morphine will be administered intravenously	Drug: Morphine; Subjects will receive Morphine while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Placebo Comparator: Placebo; Saline will be administered intravenously	Other: Placebo; Subjects will receive saline while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.

Outcome Measures

Primary Outcome Measures :

1. Tolerance to Simulated Hemorrhage [ Time Frame: 30 minutes from the onset of applying lower-body negative pressure ]
   Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and morphine limbs, by causing progressive central hypovolemia via lower-body negative pressure (LBNP). This progressive 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 LBNP 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). A larger cumulative stress index represents a greater tolerance

Secondary Outcome Measures :

1. Pain Assessment - Algometer [ Time Frame: 30 minutes from the onset of the protocol ]
   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 morphine.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

• Subjects who have cardiac, respiratory, neurological and/or metabolic illnesses
• Any known history of renal or hepatic insufficiency/disease
• Pregnancy or breast feeding
• Current smokers, as well as individuals who regularly smoked within the past 3 years
• Positive urine drug screen
• Currently taking pain modifying medication(s)

Contacts and Locations

Locations

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

  Study Documents (Full-Text)

Documents provided by Craig Crandall, University of Texas Southwestern Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] March 31, 2021

Informed Consent Form  [PDF] April 6, 2021

More Information

• Responsible Party: Craig Crandall, Professor of Internal Medicine, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT04138615
• Other Study ID Numbers: STU 092017-070
• First Posted: October 24, 2019
• Results First Posted: January 12, 2023
• Last Update Posted: January 12, 2023
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

Hemorrhage; Pathologic Processes; Morphine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents