Evaluation of Sublingual Sufentanil for Moderate to Severe Monotraumatic Pain Management in Emergency Patients: A Comparative Study with Standard Analgesic Protocols

The primary objective of this study is to determine the **efficacy** of sublingual sufentanil 30 mcg in emergency patients experiencing moderate to severe pain due to a single trauma, compared to the standard management currently employed in the department. This evaluation is conducted over a time frame from T0 to T0 + 60 minutes. The clinical relevance of this objective lies in potentially providing a more effective pain management option in emergency settings, which could enhance patient outcomes and comfort.

Secondary objectives include:

• Evaluating and comparing potential adverse effects between randomization groups, focusing on hypotension, bradycardia, respiratory depression, sweating, drowsiness, nausea and/or vomiting, and dizziness.
• Comparing the variation of pain using a verbal numerical scale at multiple time points: T0, T0 + 15 min, T0 + 30 min, T0 + 45 min, T0 + 60 min, T0 + 120 min, and T0 + 180 min.
• Comparing hemodynamic parameters such as blood pressure, pulse, oxygen saturation, and respiratory rate between randomization groups.
• Assessing the quality of pain management as perceived by the patient, both in terms of the product used and the overall pain management strategy.

The clinical trial involves participants who have experienced **trauma to the lower or upper limb** and are admitted for moderate to severe pain. The study population includes both male and female adults, with an age range that encompasses young adults to middle-aged individuals. Participants are required to have a numeric pain rating scale of 4 or higher, indicating significant pain levels. The trial excludes vulnerable populations, ensuring a focus on individuals with a Glasgow Coma Scale score of 15 and an oxygen saturation (SaO2) greater than 95% in ambient air. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the inclusion of patients with monotraumatic pain in the specified limbs, ensuring a targeted approach to evaluating the efficacy of sublingual sufentanil 30mcg compared to standard pain management practices.

The clinical trial is designed to evaluate the efficacy of **sufentanil** 30 mcg administered sublingually in emergency patients experiencing moderate to severe pain due to trauma to the lower or upper limb. The trial follows a **randomized**, **double-blind**, and **controlled** design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias. The study is categorized as low-intervention, as the use of sufentanil is within its marketing authorization, and no additional diagnostic or monitoring procedures are required beyond standard clinical practice. The trial is expected to commence recruitment on December 31, 2024, and conclude by January 1, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as being an adult patient with a numeric pain rating scale of 4 or higher, pain of monotraumatic origin in the upper or lower limb, a Glasgow Coma Scale score of 15, and oxygen saturation (SaO2) greater than 95% in ambient air. Following the screening, participants will be randomized to receive either the investigational product or a comparator. The primary endpoint is the variation in pain rating measured by the verbal numerical scale between baseline (T0) and 60 minutes post-administration (T0+60 min).

Secondary endpoints include the assessment of the tolerance profile through the occurrence of adverse events such as hypotension, bradycardia, respiratory depression, sweating, drowsiness, nausea, vomiting, and dizziness. Pain intensity will be evaluated at multiple time points: T0, T0+15 min, T0+30 min, T0+45 min, T0+60 min, T0+120 min, and T0+180 min. Hemodynamic parameters, including blood pressure, pulse, oxygen saturation, and respiratory rate, will also be monitored. At the end-of-study visit, occurring at T0+180 min, participants will provide feedback on their satisfaction with the pain management and the permucosal product tested, using a verbal satisfaction scale ranging from 0 (very dissatisfied) to 10 (very satisfied).

The expected duration of participant involvement is approximately 180 minutes, with the possibility of early termination if adverse events or other safety concerns arise. The trial aims to provide valuable insights into the management of traumatic pain in emergency settings, potentially influencing future clinical practices.

The clinical trial involves the administration of **Dzuveo**, a sublingual tablet containing **sufentanil** as the active substance. Each tablet contains 30 micrograms of sufentanil, and the maximum daily dose is 90 micrograms. The administration route is oral, specifically sublingual, allowing for rapid absorption. The treatment period is limited to a maximum of one day. This medication is being evaluated for its efficacy in managing moderate to severe pain in emergency situations.

**KETOPROFENE AGUETTANT** is used as a comparator in the trial. It is a solution for infusion containing **ketoprofen**. The pharmaceutical form is a solution for intravenous use, with a maximum daily dose of 300 mg. The treatment period is restricted to one day. This medication is utilized to compare its effectiveness against the experimental treatment.

Another comparator is **MORPHINE (CHLORHYDRATE) RENAUDIN**, a solution for injection containing **morphine hydrochloride**. It is administered intravenously, with a concentration of 10 mg/ml and a maximum daily dose of 15 mg. The treatment duration is limited to one day.

**CODOLIPRANE** is a tablet containing **paracetamol** and **codeine phosphate hemihydrate**. It is administered orally, with a maximum daily dose of 4 grams. The treatment period is one day. This combination is used as a comparator to assess its pain management efficacy.

**TRAMADOL ARROW** is a solution for injection/infusion containing **tramadol hydrochloride**. It is administered intravenously, with a maximum daily dose of 600 mg. The treatment period is one day. This medication serves as a comparator in the trial.

**ACUPAN** is a solution for injection containing **nefopam**. It is administered intravenously, with a maximum daily dose of 120 mg. The treatment period is one day. This medication is used as a comparator to evaluate its effectiveness in pain management.

**IXPRIM** is a film-coated tablet containing **tramadol hydrochloride** and **paracetamol**. It is administered orally, with a maximum daily dose of 8 units. The treatment period is one day. This combination is used as a comparator in the trial.

**KALINOX** is a medicinal gas, compressed, containing **nitrous oxide** and **oxygen**. It is administered via inhalation, with a maximum daily dose of 1 hour. The treatment period is one day. This gas mixture is used as a comparator to assess its analgesic properties.

**PARACETAMOL AGUETTANT** is a solution for infusion containing **paracetamol**. It is administered intravenously, with a maximum daily dose of 4 grams. The treatment period is one day. This medication is used as a comparator in the trial.

**DOLIPRANE** is available in two forms: a capsule and a tablet, both containing **paracetamol**. The capsule form is a hard capsule, and the tablet form is a standard tablet. Both are administered orally, with a maximum daily dose of 4 grams. The treatment period is one day. These forms are used as comparators in the trial.

The efficacy of sublingual **sufentanil** 30 mcg in managing moderate to severe monotraumatic pain in emergency situations will be assessed through a clinical trial. The primary endpoint for evaluating efficacy is the variation in pain rating, measured by the verbal numerical scale, between the initial time point (T0) and 60 minutes post-administration (T0+60 min). Secondary endpoints include the variation of pain rating at additional time intervals: T0+15 min, T0+30 min, T0+45 min, T0+60 min, T0+120 min, and T0+180 min. The trial will also assess the tolerance profile by analyzing the occurrence of adverse events such as hypotension, bradycardia, respiratory depression, sweating, drowsiness, nausea, vomiting, and dizziness.

Additional efficacy assessments will involve measuring variations in hemodynamic parameters, including blood pressure, pulse, oxygen saturation, and respiratory rate. At the conclusion of the study, at T0+180 min, patient satisfaction will be evaluated using a verbal satisfaction scale ranging from 0 ("Very dissatisfied") to 10 ("Very satisfied"). This will include an assessment of the permucosal product tested and the overall pain management. The trial is designed to ensure that the use of **sufentanil** aligns with its marketing authorization, with no additional diagnostic or monitoring procedures beyond standard clinical practice.