Trauma Acute Pain Treatment With Methoxyflurane Vaporized (PENTHROX®): Efficacy and Safety Study (MEDITA)

Mundipharma

Status and phase: Completed; Phase 3

Conditions: Acute Traumatic Pain

Treatments: Drug: Ketoprofen; Combination Product: Methoxyflurane and Penthrox inhaler; Drug: Paracetamol; Drug: Morphine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03585374

MR311-3504

Details and patient eligibility

About

The prompt treatment of pain due to minor trauma is often an unmet need in both Emergency Room Department and Ambulance Rescue. Most of the available drugs are intravenously administered and such route of administration may account for delay in the pain relief onset.

Methoxyflurane is an halogenated anesthetic, self-administered by the patient at sub-anesthetic dose through an easy to handle inhaler (Penthrox®). The efficacy and safety of Penthrox® in the treatment of acute traumatic pain will be investigated in an out-of-hospital and in hospital emergency medical care setting.

Enrollment: 272 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent must be provided by each patient prior to any study-specific activity. In cases where the patient is unable to write autonomously, it must be obtained a verbal consent in presence of a witness that the patient will have to confirm autonomously as soon as (s)he is able
• Stable, vigilant and collaborative patient i.e. able to understand and communicate with the examiner in order to carry out the study activities
• Age ≥ 18 years
• Trauma to the limbs (fracture, dislocation, crushing, bruising) in a single district.

N.B. For recruiting, given the particular setting, no instrumental confirmation is required but suspicion of involvement of a single district is sufficient.

• Moderate to severe pain, detected by the Numerical Rating Scale (NRS score ≥4)

Exclusion criteria

• Personal or family history (parents or siblings) for malignant hyperthermia.
• History of severe adverse reactions to inhaled anesthetics.
• History of renal failure
• History of liver failure.
• Trauma risky dynamics (ejection from the vehicle, cabin deformation, death of an occupant of the same vehicle, motor vehicle / pedestrian or cyclist impact with a motor vehicle in motion, projection / overturn, fall from a height of> 3 meters, extraction on event place > 20 min).
• Altered level of vigilance and / or conscience (GCS <15)
• Symptomatic hypotension or Systolic Pressure <100 mm / Hg
• Discomfort with Respiratory Rate > 20 and Oxygen Saturation <95%
• Known pregnancy status.Note: a 1 day delay with respect to the planned menstruation date (28days since the beginning of the previous one) has to be considered a suspected pregnancy.
• Hypersensitivity to methoxyflurane, to any fluorinated anesthetic or to the E321 butylhydroxytoluene excipient.
• Current treatment with any analgesic for chronic pain or in the previous 5 hours (8 hours in the case of diclofenac).
• Known allergy to both paracetamol and non-steroidal anti-inflammatory drugs or known hypersensitivity to morphine
• All types of acute abdomen and paralytic ileus
• Hearth failure
• Recent (within2 months) biliary tract surgery
• Current bronchial asthma attack
• Uncontrolled epilepsy
• Depressive state treated with Monoamine Oxidase Inhibitors (ongoing or interrupted less 3 wks ago)
• Treatment with naltrexone
• History of active or recurrent peptic ulcer/hemorrhage (2 or more episodes of documented ulceration or bleeding in the last 6 months)
• Bleeding diathesis
• Current Intensive diuretic therapy
• Chronic dyspepsia, gastritis with significant episodes in the last 2 months
• Leucopenia and thrombocytopenia, current hemorrhages
• Current anticoagulant therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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272 participants in 2 patient groups

A_test drug_Methoxyflurane (Penthrox®)

Experimental group

Description:

Pain from moderate to severe (NRS score 4-10). 3 ml of methoxyflurane vaporized through the Penthrox® inhaler. The drug is self administered under the supervision of investigators/study nurse. The treatment duration is about 25 minutes. The patient is instructed to breath normally and to close the diluter aperture via his/her forefinger to increase the analgesic effect, if needed. In case of pain increase or insufficient pain relief the investigator is allowed to administer a rescue medication as per local routine practice.

Treatment:

Combination Product: Methoxyflurane and Penthrox inhaler

B_comparator_Morphine/Paracetamol/Ketoprofen

Active Comparator group

Description:

The comparator to be administered will vary according to pain intensity and local clinical practice. In case of severe pain (NRS score ≥ 7), morphine will be administered at a dose of 0.10 mg/kg body weight. In case of moderate pain (NRS score 4-6) paracetamol or ketoprofen will be administered respectively at a 1 g and 100 mg dose. All comparator will be administered by intravenous drip in a maximum 10 minutes time of infusion. . Maximum time of infusion 10 minutes.

Treatment:

Drug: Morphine

Drug: Paracetamol

Drug: Ketoprofen