Trial Outcomes & Findings for Analgesics in the Pre-hospital Setting: Implications on Hemorrhage Tolerance - Fentanyl (NCT NCT04136548)

NCT ID: NCT04136548

Last Updated: 2022-01-24

Results Overview

Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and fentanyl 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).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

41 participants

Primary outcome timeframe

12 months

Results posted on

2022-01-24

Participant Flow

Forty-one adults enrolled by providing written and oral consent. Of these 38, three adults were deemed not to be eligible based upon screening criteria prior to randomization. Therefore, only 38 adults were 'enrolled and randomized' (see 'Participant Flow' below).

Participant milestones

Participant milestones
Measure
Placebo, Then Fentanyl
Participants first received Placebo (75 ug) each (\<5mins). After a washout period of lying down for resting for sometime , then Fentanyl (75 ug) is administered to each participant (\<5 mins)
Fentanyl, Then Placebo
Participants first received Fentanyl (75 ug) visit. each (\<5mins). After a washout period of lying down for resting for sometime , then Placebo (75 ug) is administered to each participant (\<5 mins)
Enrolled & Randomized
STARTED
19
19
Enrolled & Randomized
COMPLETED
13
15
Enrolled & Randomized
NOT COMPLETED
6
4
First Visit
STARTED
13
15
First Visit
COMPLETED
13
15
First Visit
NOT COMPLETED
0
0
Washout (at Least 48 Hours)
STARTED
13
15
Washout (at Least 48 Hours)
COMPLETED
13
15
Washout (at Least 48 Hours)
NOT COMPLETED
0
0
Second Visit
STARTED
13
15
Second Visit
COMPLETED
13
15
Second Visit
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Participants
n=41 Participants
All participants
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
41 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Sex: Female, Male
Female
22 Participants
n=5 Participants
Sex: Female, Male
Male
19 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
39 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
5 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
4 Participants
n=5 Participants
Race (NIH/OMB)
White
32 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
41 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and fentanyl 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).

Outcome measures

Outcome measures
Measure
Fentanyl
n=28 Participants
Fentanyl will be administered intravenously during one visit. Fentanyl: Subjects will receive 75 ug Fentanyl while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Placebo
n=28 Participants
Placebo (saline) will be administered intravenously during one visit. Placebo: Subjects will receive saline while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Cumulative Stress Index
647 mmHg x minutes
Standard Deviation 386
676 mmHg x minutes
Standard Deviation 295

SECONDARY outcome

Timeframe: 12 months

Population: Pressure pain tolerance was evaluated in a subset of individuals

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 fentanyl.

Outcome measures

Outcome measures
Measure
Fentanyl
n=17 Participants
Fentanyl will be administered intravenously during one visit. Fentanyl: Subjects will receive 75 ug Fentanyl while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Placebo
n=17 Participants
Placebo (saline) will be administered intravenously during one visit. Placebo: Subjects will receive saline while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Pressure Pain Tolerance
1.6 Kilograms
Interval 0.9 to 2.2
1.1 Kilograms
Interval 0.8 to 1.3

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Fentanyl

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Craig Crandall

University of Texas Southwestern Medical Center

Phone: 2143454623

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place