Efficacy and Safety of Penthrox® Combined With a Standard Analgesia (SoC) in Adult Patients Admitted to the Emergency Department With Moderate to Severe Pain Associated With Trauma
Efficacy and Safety of Penthrox® Combined With a Standard Analgesia (SoC) in Adult Patients Admitted to the Emergency Department With Moderate to Severe Pain Associated With Trauma
A phase 4 randomised, double-blind study to assess the efficacy and safety of Penthrox® used
 from the outset in multimodal analgesia, in combination with the standard analgesic protocol
 used in the department, for conscious adult patients presenting in an emergency department
 with moderate to severe pain associated with a trauma
On admission, the patient pain score will be measured using a numerical scale (NRS-11) to
 verify the eligibility of the patient in the study (NRS ≥ 4).

 At the time of randomisation, the patient's pain score will be measured using a VAS in order
 to verify the patient's eligibility for randomisation (VAS ≥ 40).

 Admissible patients will be randomised by IWRS (Interactive Web Response System) to receive:

 -  Either Penthrox® + SoC

 -  Or placebo + SoC (Figure 1). Randomisation will be stratified by sex, site and according
 to the baseline pain score (NRS 4-5 for a moderate-intensity pain versus NS 6-10 for a
 severe-intensity pain).

 The IWRS system will be based on the fact of including 50% patients with moderate pain and
 50% patients with severe pain.

 Close weekly monitoring of this ratio will be set up. The decision to no longer include
 patients in one of the study subgroups according to pain, if necessary, or to change this
 ratio, will be made by the Study Sponsor and in agreement with the study
 investigator-coordinator and the study scientific committee. A minimum of 150 patients will
 be included in the severe pain subgroup (EN 6-10).

 The treatment (preparation of two inhalers, the second only being given to the patient on
 request) will only be administered once intermittently or continuously to patients on
 admission to the study (D0, T0).

 The pain score will be assessed using the VAS every 5 minutes up to 20 minutes, then at 30,
 60, 90, and 120 minutes after the start of study treatment (T0). Patients will be assessed
 until their discharge from the emergency departments (hospitalization, transfer home,
 transfer to the operating room) or up to 120 minutes after the initial administration.

 A telephone interview will take place 14 (± 2) days after the first treatment administration
 to assess the medium-term safety of the product.
Inclusion Criteria:

 -  Men and women aged 18 or older

 -  Patients (in an emergency, parent or relative) who dated and signed their informed
 consent to participate in the study

 -  Patients admitted to the emergency department due to a trauma

 -  Patients having a pain score ≥ 4 measured using a numerical scale (NRS) at the time of
 admission to emergency departments.

 -  Patients having a pain score ≥ 40 measured using the VAS at the time of randomisation.

 Exclusion Criteria:

 -  Life-threatening conditions requiring immediate admission to the operating theatre or
 the intensive care unit;

 -  Impaired consciousness according to the investigator regardless of the cause,
 including head trauma or drug or alcohol consumption;

 -  Acute medicinal or alcohol intoxication, according to the investigator;

 -  Pregnant woman or woman at risk of pregnancy and not using highly effective
 contraception methods or known lactation;

 -  Analgesic treatment within 5 hours (8 h for sodium diclofenac) prior to admission,
 except for paracetamol, which is allowed;

 -  Treatment with nitrous oxide within 5 hours before presentation at the emergency
 department;

 -  Use of analgesics for chronic pain;

 -  Prior use of Penthrox®;

 -  Use of an investigational product one month before presentation at the emergency
 department;

 -  Hypersensitivity to Penthrox® or any other fluoridated anesthetic;

 -  History of signs of hepatic lesions after use of methoxyflurane or after anaesthesia
 by a halogenated hydrocarbon;

 -  Malignant hyperthermia: Known malignant hyperthermia or patient genetic predisposition
 or patient or family history of serious adverse reactions;

 -  Clinical evidence of respiratory depression according to the investigator;

 -  Clinical evidence of cardiovascular instability according to the investigator;

 -  Clinical renal or hepatic damage, according to the investigator, pre-existing or
 known;

 -  Presence of any other clinical condition that can, according to the investigator's
 opinion, have an impact on the patient's ability to participate in the study or the
 results of the study.

 -  Individuals protected by law