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Completed

NCT Number: NCT03585374

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

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.

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Key information

Conditions

Acute Traumatic Pain Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

AO Universitaria- Policlinico V.Emanuele Medicina e Chirurgia d'Accettazione e d'Urgenza, Catania, CT, Italy

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Methoxyflurane and Penthrox inhaler

Combination Product

3ml of methoxyflurane vaporized through an inhaler (Penthrox). Inhalation, by regular breathing, last about 25 minutes.

Other names: Penthrox

Morphine

Drug

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.

Other names: Morphine for intravenous use

Paracetamol

Drug

Each site will use the commercial available product already in use as per local clinical practice. The drug will be intravenously administered at a 1 g dose The time of infusion should be not longer than 10 minutes.

Other names: Paracetamol for intravenous use

Ketoprofen

Drug

Each site will use the commercial available product already in use as per local clinical practice. The drug will be intravenously administered at a 100 mg dose. The time of infusion should be not longer than 10 minutes.

Other names: Ketoprofen for intravenous use

Primary outcomes

  1. Change in the intensity of pain within 10 minutes.

    Time frame: From baseline up to 10 minutes later.

    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.

Secondary outcomes

  1. Need for rescue medication.

    Time frame: From baseline up to 30 minutes later.

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

  2. Change in the intensity of pain within 30 minutes.

    Time frame: From baseline up to 30 minutes later.

    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).

  3. Time to pain relief.

    Time frame: From baseline up to 30 minutes.

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

  4. Global assessment of treatment efficacy perceived by the patient.

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

    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.

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

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

    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.

  6. Need for dilution hole closure (only Experimental Arm).

    Time frame: From baseline up to 30 minutes later.

    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.

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

    Time frame: From baseline up to 30 minutes later.

    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).

  8. Incidence of Treatment-Emergent Adverse Events (AE)

    Time frame: From baseline up to 16 days later.

    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.

  9. Change in pulse rate

    Time frame: From baseline up to 30 minutes later.

    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.

  10. Change in blood pressure

    Time frame: From baseline up to 30 minutes later.

    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.

  11. Change in respiration rate

    Time frame: From baseline up to 30 minutes later.

    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.

  12. Incidence of treatment-emergent pregnancy

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

    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.

  13. Incidence of investigational medicinal drug misuse/abuse

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

    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.

Sponsors and collaborators

Lead sponsor

Mundipharma Pharmaceuticals srl

Industry

Collaborators

  • Bioikos Ambiente Srl

Registry information

Official study 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

Acronym: MEDITA

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jul 13, 2018
Registry last updated
May 9, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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