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

Mundipharma Pharmaceuticals srl272 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

272

Conditions

Acute Traumatic Pain

Interventions

Methoxyflurane and Penthrox inhaler

MorphineDRUG

Each site will use the commercial available product already in use as per local clinical practice. The drug will be intravenously administered at a dose of 0.10 mg/Kg body weight. The time of infusion should be not longer than 10 minutes.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (16)

AO Universitaria- Policlinico V.Emanuele Medicina e Chirurgia d'Accettazione e d'Urgenza

Catania, CT, Italy

AO per l'Emergenza- Cannizzaro UO Servizio di Urgenza Emergenza Sanitaria 118

Catania, CT, Italy

Medicina D'Urgenza ed Accettazione Azienda Ospedaliera di Catanzaro "Pugliese-Ciaccio"

Catanzaro, CZ, Italy

Azienda USL della Romagna - Forlì Unità Operativa Pronto Soccorso, Medicina d'Urgenza, 118

Forlì, FC, Italy

Azienda Sanitaria di Firenze Ospedale Santa Maria Annunziata DEA -Medicina D'Urgenza

Bagno a Ripoli, FI, Italy

AUSL della ROMAGNA Ospedale M. Bufalini Pronto Soccorso - Medicina d'Urgenza

Cesena, Forlì-Cesena, Italy

IRCCS San Martino Servizio 118

Genova, GE, Italy

Istituto Clinico Humanitas - Pneumologia e Medicina d'urgenza

Rozzano, Milan, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Dipartimento di Anestesia e Terapia Intensiva Donna-Bambino

Milan, MI, Italy

ULSS 6 EUGANEA ex Ulss 16 Pronto Soccorso e Medicina d'Urgenza Ospedale S. Antonio

Padua, PD, Italy

...and 6 more locations

Outcomes

Primary Outcomes

Change in the intensity of pain within 10 minutes.

The change in the pain intensity occurring from baseline (patient randomization) up to 10 minutes later. The pain intensity is measured by a 100 mm Visual-Analogic Scale (VAS). The pain intensity is measured at the baseline and after 3, 5, 10 minutes and the difference with the baseline measure is calculated. The changes (differences) from baseline will be compared between the two arms regardless the class of intensity pain (moderate + severe) and for the class of moderate pain.

Time frame: From baseline up to 10 minutes later.

Secondary Outcomes

Need for rescue medication.

Percentage of patients who are using rescue medication for insufficient or unsatisfactory therapeutic effect of the trial drugs.

Time frame: From baseline up to 30 minutes later.

Change in the intensity of pain within 30 minutes.

The change in the pain intensity occurring from baseline up to 30 minutes later. The pain intensity is measured by a 100 mm Visual-Analogic Scale (VAS). The pain intensity is measured after 15, 20, 25, 30 minutes from baseline and the difference with the baseline measure is calculated. The changes (differences) from baseline will be compared between the two arms regardless the class of intensity pain (moderate + severe).

Time frame: From baseline up to 30 minutes later.

Time to pain relief.

Time to get relief from pain starting from randomization. The patient will be asked to refer when he/she feel better.

Time frame: From baseline up to 30 minutes.

Global assessment of treatment efficacy perceived by the patient.

30 minutes after randomization the patient will be asked to rate according to a 5 levels Likert scale (poor, moderate, good, very good, excellent) the global efficacy of the treatment.

Time frame: From baseline to 30 minutes later or to the end of the treatment (whichever occurs first).

Global assessment of treatment practicality in the investigator's opinion.

30 minutes after randomization the treating investigator will be asked to rate according to a 5 levels Likert scale (poor, moderate, good, very good, excellent) the practicality of the administered treatment.

Time frame: From baseline to 30 minutes later or to the end of the treatment (whichever occurs first).

Need for dilution hole closure (only Experimental Arm).

The closure of the dilution hole of the Penthrox device increases the inhalated amount of methoxyflurane and its antalgic effect. The patient will be instructed about the chance to close that hole and will be asked to refer the occurrence.

Time frame: From baseline up to 30 minutes later.

Change in the intensity of pain within 30 minutes by trauma type.

The change in the pain intensity occurring from baseline (patient randomization) up to 30 minutes later. The pain intensity is measured by a 100 mm Visual-Analogic Scale (VAS). The pain intensity is measured at the baseline and after 3, 5, 10, 15, 20, 25, 30 minutes and the difference with the baseline measure is calculated. The changes (differences) from baseline to each of the following timepoints for each trauma type will be compared between the two arms regardless the class of intensity pain (moderate + severe).

Time frame: From baseline up to 30 minutes later.

Incidence of Treatment-Emergent Adverse Events (AE)

Each untoward clinical event not related, in the Investigator judgement, to the underlying patient inclusion condition (trauma) will be recorded. Seriousness, relationship with the investigational drug, action taken for AE treatment will recorded for each AE.

Time frame: From baseline up to 16 days later.

Change in pulse rate

The pulse rate (beats/min) will be measured (either manually or automatically) at baseline and 10, 30 minutes later. The difference between the baseline values and the following ones will be calculated.

Time frame: From baseline up to 30 minutes later.

Change in blood pressure

The Blood Systolic and Diastolic pressure (mmHg) will be measured at baseline and 10, 30 minutes later. The difference between the baseline values and the following ones will be calculated.

Time frame: From baseline up to 30 minutes later.

Change in respiration rate

The respiration rate (breaths/min) will be measured (either manually or automatically) at baseline and 10, 30 minutes later. The difference between the baseline values and the following ones will be calculated.

Time frame: From baseline up to 30 minutes later.

Incidence of treatment-emergent pregnancy

Pregnant patients or suspected to be pregnant are excluded from the trial. In case of occurrence the pregnancy will be recorded and followed up until delivery for pharmacovigilance purposes.

Time frame: From baseline up to 16 days later. The follow-up until delivery is out from the scope of the trial.

Incidence of investigational medicinal drug misuse/abuse

The occurrence of Investigational medicinal drug abuse (persistent or sporadic, intentional excessive use of medicinal products which is accompanied by harmful physical or psychological effects) or misuse (intentionally and inappropriately use not in accordance with the prescribed dose) during the treatment phase will be recorded.

Time frame: From baseline up to 30 minutes later or to the end of the treatment (whichever occurs first).