DSUVIA Early Evaluation of Pain Trial

• Sufentanil 30 MCG Sublingual Tablet (Drug): 30 microgram sublingual tablet administered using sublingual applicator
• standard care pain treatment (Drug): standard care pain treatment given in Emergency Department

Primary outcomes

• Verbally Administered Numeric Rating Scale (VNRS) [30 minutes after administration]: Verbally administered Numeric Rating Scale (VNRS) for clinical pain measurement (scale of 0-100, where 0 is having no pain)

Secondary outcomes

• Verbally Administered Numeric Rating Scale (VNRS) [Every 30 min from 30 min post administration until the time of ED discharge or rescue narcotic administered and up to 120 minutes after administration, whichever comes first]: Verbally administered Numeric Rating Scale (VNRS) for clinical pain measurement (scale of 0-100, where 0 is having no pain)
• Patient Global Assessment (PGA) of Pain Control [every 30 minutes after administration until the time of ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes after administration)]: An assessment of the patient's pain, made by the patient themselves, made at 30 minute intervals up to 120 min after the intervention, or until discharge, or administration of rescue medication
• Time-weighted Summed Pain Intensity Difference (SPID) @ 30, 60, 90, 120 Min [every 30 minutes after administration until ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes after administration)]: time-weighted Summed Pain Intensity Difference (SPID) is a statistical measure that calculates the cumulative pain reduction over a period of time by summing up the differences between baseline pain and current pain at various time points. The range for the SPID is 0-100 per time point, A score of 0 indicates no pain, a score of 100 indicating the worst pain intensity difference. Some patients did not participate in the SPID due to discharge or requiring rescue narcotic administration.
• Number of Participants Who Needed Rescue Narcotic Doses [at 30 minutes following administration and during ED stay (up to 120 minutes)]: Count of patients requiring additional pain medication after recieving the intervention (sufentanil) or the standard care control.
• Patient Cognitive Function as Assessed by Six Item Screener (SIS) [at 30 minutes following administration]: The Six Item Screener (SIS) is a simple assessment of cognitive impairment. It asks 6 questions, 3 based on recall and 3 based on orientation, each question is worth 1 point. The score can range between 0 and 6 correct answers. Higher numbers of correct answers indicated better outcomes (less cognitive impairment). Fewer patients were able to complete the SIS questionnaire then were enrolled in the study as some were discharged, received rescue medication or declined to participate prior to administration of the survey.
• Healthcare Professional Global Assessment (HPGA) of Method of Pain Control [at 30 minutes following administration]: Acceptability of pain treatment to health care providers based on a subjective assessment of the patients facial expressions, behavior, physical presentation and reported pain level. Nurses caring for the participant following treatment with the study drug were asked to characterize their patients pain relief as Poor, Fair, Good or Excellent.
• Number of Participants With Hypoxia Needing Supplemental Oxygen [from administration to ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes)]: The number of patients with an SpO2 less than 90 percent receiving supplemental oxygen
• Number of Participants With Hypotension [from administration to ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes)]: systolic blood pressure less than 90mmHg
• Number of Participants With Nausea [from administration to ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes)]
• Number of Participants With Vomiting [from administration to ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes)]
• Number of Participants With Headache [from administration to ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes)]
• Number of Participants With Dizziness Requiring Treatment [from administration to ED discharge or rescue narcotic administered, whichever comes first (up to 120 minutes)]: Dizziness requiring treatment
• Number of Participants Who Had a 10 Point Reduction in VNRS Score @30 Min Intervals to 120min [Time to a 10 point reduction in VNRS following administration of study drug. Participants were followed to 120 min or discharge in 30 min intervals]: The Number of participants that had a 10 point reduction in their VNRS @ 30min intervals to 120min
• Number of Participants With Need for Bag Valve Mask Ventilation or Advanced Airway Management [From drug administration up to 120 min following administration]: Need for advanced airway or bag valve mask ventilation
• Richmond Agitation-Sedation Scale (RASS) [Assessed at 30 minutes after administration]: The Richmond Agitation-Sedation Scale is scored from a -5 (unresponsive) to +4 (combative) with 0 being alert and calm.
• Richmond Agitation-Sedation Scale (RASS) @ 60 Min [RASS @ 60 min]: The Richmond Agitation-Sedation Scale is scored from a -5 (unresponsive) to +4 (combative) with 0 being alert and calm. Fewer patients were able to complete the SIS questionnaire then were enrolled in the study as some were discharged, received rescue medication or declined to participate prior to administration of the survey.
• Richmond Agitation-Sedation Scale (RASS) @ 90 Min [RASS @ 90 minutes]: The Richmond Agitation-Sedation Scale is scored from a -5 (unresponsive) to +4 (combative) with 0 being alert and calm.Fewer patients were able to complete the SIS questionnaire then were enrolled in the study as some were discharged, received rescue medication or declined to participate prior to administration of the survey.
• Richmond Agitation-Sedation Scale (RASS) @ 120 Min [RASS @ 120 min]: The Richmond Agitation-Sedation Scale is scored from a -5 (unresponsive) to +4 (combative) with 0 being alert and calm. Fewer patients were able to complete the SIS questionnaire then were enrolled in the study as some were discharged, received rescue medication or declined to participate prior to administration of the survey.

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Trauma activation (Level I, II or III)
2. Age 18-70 years inclusive
3. Need for pain treatment based upon NRS (0-100) clinical pain measurement ≥ 50
4. Estimated time in Emergency Department > 30 minutes following informed consent

Exclusion Criteria:

1. Advanced airway management prior to 1st dose administration
2. Known allergy to opioids
3. Known prisoner
4. Known pregnancy
5. ED pain medication contraindicated
6. Significant respiratory depression
7. Known or suspected gastrointestinal obstruction, including paralytic ileus

Participant flow

Outcome results

• Verbally Administered Numeric Rating Scale (VNRS) (Primary), Mean, units on a scale: DSUVIA (Sufentanil) 68 +/- 27; Standard Care 66 +/- 23 (p 0.56)
• Verbally Administered Numeric Rating Scale (VNRS) (Secondary), Mean, units on a scale: DSUVIA (Sufentanil) 68 +/- 27; Standard Care 66 +/- 23 (p 0.18)
• Patient Global Assessment (PGA) of Pain Control (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 22; Standard Care 12 (p 0.005)
• Time-weighted Summed Pain Intensity Difference (SPID) @ 30, 60, 90, 120 Min (Secondary), Mean, units on a scale: DSUVIA (Sufentanil) 6 +/- 10; Standard Care 7 +/- 10 (p 0.39)
• Number of Participants Who Needed Rescue Narcotic Doses (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 27; Standard Care 29 (p 0.64)
• Patient Cognitive Function as Assessed by Six Item Screener (SIS) (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 20; Standard Care 22 (p 0.61)
• Healthcare Professional Global Assessment (HPGA) of Method of Pain Control (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 14; Standard Care 5 (p 0.009)
• Number of Participants With Hypoxia Needing Supplemental Oxygen (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 4; Standard Care 4 (p 0.96)
• Number of Participants With Hypotension (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 1; Standard Care 1
• Number of Participants With Nausea (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 5; Standard Care 3
• Number of Participants With Vomiting (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 3; Standard Care 0
• Number of Participants With Headache (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 1; Standard Care 2
• Number of Participants With Dizziness Requiring Treatment (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 0; Standard Care 1 (p >0.99)
• Number of Participants Who Had a 10 Point Reduction in VNRS Score @30 Min Intervals to 120min (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 28; Standard Care 36 (p 0.90)
• Number of Participants With Need for Bag Valve Mask Ventilation or Advanced Airway Management (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 0; Standard Care 0
• Richmond Agitation-Sedation Scale (RASS) (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 0; Standard Care 0 (p 0.99)
• Richmond Agitation-Sedation Scale (RASS) @ 60 Min (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 0; Standard Care 0 (p 0.84)
• Richmond Agitation-Sedation Scale (RASS) @ 90 Min (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 0; Standard Care 0 (p 0.81)
• Richmond Agitation-Sedation Scale (RASS) @ 120 Min (Secondary), Count of participants, Participants: DSUVIA (Sufentanil) 0; Standard Care 0 (p 0.74)

Adverse events

Time frame: Adverse events were collected up to 120 minutes after administration of the study drug

Serious adverse events by term

Other adverse events by term

Limitations and caveats: Our study is a first of its kind comparing sublingual sufentanil to standard care in trauma patients. The intervention could not be blinded which imparts bias. This study was conducted at two level 1 trauma centers in the city of Pittsburgh and while the population was typical of our region, it may not be broadly generalizable. We did not dictate the choice or dose of analgesic in the standard arm. There was missingness in the data and no primary outcome was recorded in 20 subjects.

• Results publication: Guyette FX, Chaudhary P, Vincent LE, Love ET, Brubaker DP, Neal MD, Brown JB, Rixe J, Barton DJ, Yates A, Wisniewski SR, Sperry JL. A Randomized Controlled Trial of Sublingual Sufentanil in Early Management of Pain in Trauma. Anesth Analg. 2025 Jul 1;141(1):172-180. doi: 10.1213/ANE.0000000000007384. Epub 2025 Feb 7. PMID 39919020

• Study Protocol and Statistical Analysis Plan (PDF, 2023-01-12)
• Informed Consent Form (PDF, 2023-12-18)

• Jason Sperry, MD, Study director, University of Pittsburgh