Clinical trial NCT03798899: 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
Official title: Multicentre, Randomised, Double-blind Study Assessing the Efficacy and Safety of Penthrox® Combined With a Standard Analgesia (SoC) in Comparison to a Placebo Combined With a Standard Analgesia (SoC) in Adult Patients Admitted to the Emergency Department With Moderate to Severe Pain Associated With Trauma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Acute
Lead sponsor: Mundipharma SAS
Sponsor class: INDUSTRY
Collaborators: name: AXONAL
name: Exystat
First posted: 2019-01-10
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: time until pain relief defined by the duration between the start of the study treatment (T0) and pain relief
timeFrame: through study completion, maximum of 2 hours
Secondary outcomes:
measure: Duration between the start of study treatment (T0) and pain relief reported by the patient
timeFrame: through study completion, maximum of 2 hours
measure: Absolute Pain Intensity Difference (PID) measured using the PI-VAS at 5, 10, 15, 20 and 30 minutes after T0
timeFrame: baseline to 5, 10, 15, 20 and 30 minutes
measure: Relative Pain Intensity Difference measured using the PI-VAS at 5, 10, 15, 20 and 30 minutes after T0
timeFrame: baseline to 5, 10, 15, 20 and 30 minutes
measure: Pain relief defined by pain intensity < 40 mm on the PI-VAS scale at 5, 10, 15, 20 and 30 minutes after T0
timeFrame: baseline to 5, 10, 15, 20 and 30 minutes
measure: Response defined by pain reduction of 20 mm on the PI-VAS at 5, 10, 15, 20 and 30 minutes after T0
timeFrame: baseline to 5, 10, 15, 20 and 30 minutes
measure: Response defined by pain reduction of 30% mm on the PI-VAS at 5, 10, 15, 20 and 30 minutes after T0
timeFrame: baseline to 5, 10, 15, 20 and 30 minutes
measure: Summed Pain Intensity Difference (SPID) measured on the PI-VAS at 5, 10, 15, 20 and 30 minutes
timeFrame: baseline to 30 minutes
measure: Proportion of patients attaining an SPID of at least 33%
timeFrame: through study completion, maximum of 2 hours
measure: Quantity of opioids received (in milligrams of morphine)
timeFrame: through study completion, maximum of 2 hours
measure: Description of the Standard of Care and concomitant analgesic treatments
timeFrame: through study completion, maximum of 2 hours
measure: Sedation score (Ramsay scale)
timeFrame: through study completion, maximum of 2 hours
measure: Patient satisfaction score (Likert 0-5 scale)
timeFrame: through study completion, maximum of 2 hours
measure: Physician satisfaction scale (Likert 0-5 scale)
timeFrame: through study completion, maximum of 2 hours
measure: Nurse satisfaction scale (Likert 0-5 scale)
timeFrame: through study completion, maximum of 2 hours
measure: Length of stay (LOS) in emergency
timeFrame: through study completion, maximum of 2 hours
measure: Assess the time until medical decision to discharge
timeFrame: through study completion, maximum of 2 hours
measure: Incidence of adverse events (AE) not associated with the underlying trauma and occurring during treatment
timeFrame: through study completion, maximum of 2 hours
measure: Change in blood pressure
timeFrame: baseline to 30 minutes
measure: Change in oxygen saturation
timeFrame: baseline to 30 minutes
measure: Change in respiration rate
timeFrame: baseline to 30 minutes
measure: Change in heart rate
timeFrame: baseline to 30 minutes
measure: Incidence of tachycardia, hypotension, hypertension and respiratory depression
timeFrame: through study completion, maximum of 2 hours
measure: Incidence of premature withdrawal of patients for safety or tolerability reasons
timeFrame: through study completion, maximum of 2 hours
Other outcomes:
Locations:
city: Annecy
country: France
facility: CH Annecy Genevois
city: Beaumont-sur-Oise
country: France
facility: GH Carnelle Porte de l'Oise
city: Bobigny
country: France
facility: Hôpital Avicenne - APHP
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Pierre Bénite
country: France
facility: Hospice civil de Lyon
city: Pontoise
country: France
facility: CH René Dubos
city: Toulouse
country: France
facility: CHU Purpan
Study officials:
affiliation: CHG Pontoise / SAMU 95
name: A Ricard-Hibon, Dr
role: PRINCIPAL_INVESTIGATOR
References: