Clinical trial NCT03585374: Trauma Acute Pain Treatment With Methoxyflurane Vaporized (PENTHROX®): Efficacy and Safety Study (MEDITA)
Official title: Efficacy and Safety of Methoxyflurane Vaporized (PENTHROX®) in the Treatment of Acute Trauma Pain in Pre-hospital Setting and in the Emergency Department in Italy: a Multicentre, Randomized, Controlled, Open-label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Traumatic Pain
Keywords: pain
methoxyflurane
Penthrox
Lead sponsor: Mundipharma Pharmaceuticals srl
Sponsor class: INDUSTRY
Collaborators: name: Bioikos Ambiente Srl
First posted: 2018-07-13
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients will be randomly assigned to Penthrox (test group) or standard analgesic treatment (comparison group). As per local clinical practice, the standard analgesic will vary according to pain intensity score measured by Numerical Rating Scale (NRS): morphine, in case of score ≥ 7 or paracetamol/ketoprofen in case of score 4-6. Penthrox treatment will be performed by inhalatory route and will last maximum 25 minutes. the standard of care will be administered by an intravenous drip lasting at maximum 10 minutes.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in the intensity of pain within 10 minutes.
timeFrame: From baseline up to 10 minutes later.
Secondary outcomes:
measure: Need for rescue medication.
timeFrame: From baseline up to 30 minutes later.
measure: Change in the intensity of pain within 30 minutes.
timeFrame: From baseline up to 30 minutes later.
measure: Time to pain relief.
timeFrame: From baseline up to 30 minutes.
measure: Global assessment of treatment efficacy perceived by the patient.
timeFrame: From baseline to 30 minutes later or to the end of the treatment (whichever occurs first).
measure: Global assessment of treatment practicality in the investigator's opinion.
timeFrame: From baseline to 30 minutes later or to the end of the treatment (whichever occurs first).
measure: Need for dilution hole closure (only Experimental Arm).
timeFrame: From baseline up to 30 minutes later.
measure: Change in the intensity of pain within 30 minutes by trauma type.
timeFrame: From baseline up to 30 minutes later.
measure: Incidence of Treatment-Emergent Adverse Events (AE)
timeFrame: From baseline up to 16 days later.
measure: Change in pulse rate
timeFrame: From baseline up to 30 minutes later.
measure: Change in blood pressure
timeFrame: From baseline up to 30 minutes later.
measure: Change in respiration rate
timeFrame: From baseline up to 30 minutes later.
measure: Incidence of treatment-emergent pregnancy
timeFrame: From baseline up to 16 days later. The follow-up until delivery is out from the scope of the trial.
measure: Incidence of investigational medicinal drug misuse/abuse
timeFrame: From baseline up to 30 minutes later or to the end of the treatment (whichever occurs first).
Other outcomes:
Locations:
city: Catania
country: Italy
facility: AO Universitaria- Policlinico V.Emanuele Medicina e Chirurgia d'Accettazione e d'Urgenza
state: CT
city: Catania
country: Italy
facility: AO per l'Emergenza- Cannizzaro UO Servizio di Urgenza Emergenza Sanitaria 118
state: CT
city: Catanzaro
country: Italy
facility: Medicina D'Urgenza ed Accettazione Azienda Ospedaliera di Catanzaro "Pugliese-Ciaccio"
state: CZ
city: Forlì
country: Italy
facility: Azienda USL della Romagna - Forlì Unità Operativa Pronto Soccorso, Medicina d'Urgenza, 118
state: FC
city: Bagno A Ripoli
country: Italy
facility: Azienda Sanitaria di Firenze Ospedale Santa Maria Annunziata DEA -Medicina D'Urgenza
state: FI
city: Cesena
country: Italy
facility: AUSL della ROMAGNA Ospedale M. Bufalini Pronto Soccorso - Medicina d'Urgenza
state: Forlì-Cesena
city: Genova
country: Italy
facility: IRCCS San Martino Servizio 118
state: GE
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas - Pneumologia e Medicina d'urgenza
state: Milan
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Dipartimento di Anestesia e Terapia Intensiva Donna-Bambino
state: MI
city: Padova
country: Italy
facility: ULSS 6 EUGANEA ex Ulss 16 Pronto Soccorso e Medicina d'Urgenza Ospedale S. Antonio
state: PD
city: Faenza
country: Italy
facility: OSPEDALE DI FAENZA Pronto Soccorso - Medicina d'Urgenza
state: Ravenna
city: Sassari
country: Italy
facility: AOU (Azienda Ospedaliera Universitaria) Sassari Unità Operativa Complessa Medicina d'Accettazione e d'Urgenza - P.S. - O.B.I.
state: SS
city: Sassari
country: Italy
facility: ATS (Azienda tutela Salute)_Struttura Complessa Centrale Operativa 118
state: SS
city: Torino
country: Italy
facility: Medicina e Chirurgia di accettazione e di urgenza Humanitas Gradenigo - Presidio Sanitario
state: TO
city: Pistoia
country: Italy
facility: Azienda USL Toscana Centro U.O. Centrale Operativa 118
city: Rimini
country: Italy
facility: AUSL della ROMAGNA Ospedale degli Infermi U.O. Pronto Soccorso - Medicina d'Urgenza
Study officials:
affiliation: Azienda Sanitaria di Firenze Ospedale Santa Maria Annunziata DEA -Medicina D'Urgenza
name: Germana Ruggiano, Dr
role: PRINCIPAL_INVESTIGATOR
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citation: Serra S, Voza A, Ruggiano G, Fabbri A, Bonafede E, Sblendido A, Soldi A, Farina A; MEDITA Study Group. Efficacy, Practicality, and Safety of Inhaled Methoxyflurane in Elderly Patients with Acute Trauma Pain: Subgroup Analysis of a Randomized, Controlled, Multicenter, Open-Label Trial (MEDITA). J Pain Res. 2020 Jul 16;13:1777-1784. doi: 10.2147/JPR.S255532. eCollection 2020.
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citation: Fabbri A, Carpinteri G, Ruggiano G, Bonafede E, Sblendido A, Farina A, Soldi A; MEDITA Study Group. Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA). Adv Ther. 2019 Jan;36(1):244-256. doi: 10.1007/s12325-018-0830-x. Epub 2018 Nov 22.