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

NCT ID: NCT03585374

Last Updated: 2019-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

272 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-08

Study Completion Date

2019-02-22

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Traumatic Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A_test drug_Methoxyflurane (Penthrox®)

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.

Group Type EXPERIMENTAL

Methoxyflurane and Penthrox inhaler

Intervention Type COMBINATION_PRODUCT

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

B_comparator_Morphine/Paracetamol/Ketoprofen

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.

Group Type ACTIVE_COMPARATOR

Morphine

Intervention Type 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.

Paracetamol

Intervention Type 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.

Ketoprofen

Intervention Type 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.

Interventions

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Methoxyflurane and Penthrox inhaler

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

Intervention Type COMBINATION_PRODUCT

Morphine

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.

Intervention Type DRUG

Paracetamol

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.

Intervention Type DRUG

Ketoprofen

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.

Intervention Type DRUG

Other Intervention Names

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Penthrox Morphine for intravenous use Paracetamol for intravenous use Ketoprofen for intravenous use

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bioikos Ambiente Srl

OTHER

Sponsor Role collaborator

Mundipharma Pharmaceuticals srl

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Germana Ruggiano, Dr

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Catania, CT, Italy

Site Status

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

Catania, CT, Italy

Site Status

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

Catanzaro, CZ, Italy

Site Status

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

Forlì, FC, Italy

Site Status

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

Bagno a Ripoli, FI, Italy

Site Status

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

Cesena, Forlì-Cesena, Italy

Site Status

IRCCS San Martino Servizio 118

Genova, GE, Italy

Site Status

Istituto Clinico Humanitas - Pneumologia e Medicina d'urgenza

Rozzano, Milan, Italy

Site Status

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

Milan, MI, Italy

Site Status

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

Padua, PD, Italy

Site Status

OSPEDALE DI FAENZA Pronto Soccorso - Medicina d'Urgenza

Faenza, Ravenna, Italy

Site Status

AOU (Azienda Ospedaliera Universitaria) Sassari Unità Operativa Complessa Medicina d'Accettazione e d'Urgenza - P.S. - O.B.I.

Sassari, SS, Italy

Site Status

ATS (Azienda tutela Salute)_Struttura Complessa Centrale Operativa 118

Sassari, SS, Italy

Site Status

Medicina e Chirurgia di accettazione e di urgenza Humanitas Gradenigo - Presidio Sanitario

Torino, TO, Italy

Site Status

Azienda USL Toscana Centro U.O. Centrale Operativa 118

Pistoia, , Italy

Site Status

AUSL della ROMAGNA Ospedale degli Infermi U.O. Pronto Soccorso - Medicina d'Urgenza

Rimini, , Italy

Site Status

Countries

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Italy

References

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Todd KH, Ducharme J, Choiniere M, Crandall CS, Fosnocht DE, Homel P, Tanabe P; PEMI Study Group. Pain in the emergency department: results of the pain and emergency medicine initiative (PEMI) multicenter study. J Pain. 2007 Jun;8(6):460-6. doi: 10.1016/j.jpain.2006.12.005. Epub 2007 Feb 15.

Reference Type BACKGROUND
PMID: 17306626 (View on PubMed)

Guru V, Dubinsky I. The patient vs. caregiver perception of acute pain in the emergency department. J Emerg Med. 2000 Jan;18(1):7-12. doi: 10.1016/s0736-4679(99)00153-5.

Reference Type BACKGROUND
PMID: 10645828 (View on PubMed)

Brown JC, Klein EJ, Lewis CW, Johnston BD, Cummings P. Emergency department analgesia for fracture pain. Ann Emerg Med. 2003 Aug;42(2):197-205. doi: 10.1067/mem.2003.275.

Reference Type BACKGROUND
PMID: 12883507 (View on PubMed)

Rupp T, Delaney KA. Inadequate analgesia in emergency medicine. Ann Emerg Med. 2004 Apr;43(4):494-503. doi: 10.1016/j.annemergmed.2003.11.019.

Reference Type BACKGROUND
PMID: 15039693 (View on PubMed)

Berben SA, Schoonhoven L, Meijs TH, van Vugt AB, van Grunsven PM. Prevalence and relief of pain in trauma patients in emergency medical services. Clin J Pain. 2011 Sep;27(7):587-92. doi: 10.1097/AJP.0b013e3182169036.

Reference Type BACKGROUND
PMID: 21505324 (View on PubMed)

Dale J, Bjornsen LP. Assessment of pain in a Norwegian Emergency Department. Scand J Trauma Resusc Emerg Med. 2015 Oct 29;23:86. doi: 10.1186/s13049-015-0166-3.

Reference Type BACKGROUND
PMID: 26514633 (View on PubMed)

Mills AM, Shofer FS, Chen EH, Hollander JE, Pines JM. The association between emergency department crowding and analgesia administration in acute abdominal pain patients. Acad Emerg Med. 2009 Jul;16(7):603-8. doi: 10.1111/j.1553-2712.2009.00441.x. Epub 2009 Jun 22.

Reference Type BACKGROUND
PMID: 19549018 (View on PubMed)

Pines JM, Hollander JE. Emergency department crowding is associated with poor care for patients with severe pain. Ann Emerg Med. 2008 Jan;51(1):1-5. doi: 10.1016/j.annemergmed.2007.07.008. Epub 2007 Oct 25.

Reference Type BACKGROUND
PMID: 17913299 (View on PubMed)

Dayan AD. Analgesic use of inhaled methoxyflurane: Evaluation of its potential nephrotoxicity. Hum Exp Toxicol. 2016 Jan;35(1):91-100. doi: 10.1177/0960327115578743. Epub 2015 Apr 28.

Reference Type BACKGROUND
PMID: 25926525 (View on PubMed)

Tomi K, Mashimo T, Tashiro C, Yagi M, Pak M, Nishimura S, Nishimura M, Yoshiya I. Alterations in pain threshold and psychomotor response associated with subanaesthetic concentrations of inhalation anaesthetics in humans. Br J Anaesth. 1993 Jun;70(6):684-6. doi: 10.1093/bja/70.6.684.

Reference Type BACKGROUND
PMID: 8329263 (View on PubMed)

Coffey F, Wright J, Hartshorn S, Hunt P, Locker T, Mirza K, Dissmann P. STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. Emerg Med J. 2014 Aug;31(8):613-8. doi: 10.1136/emermed-2013-202909. Epub 2014 Apr 17.

Reference Type BACKGROUND
PMID: 24743584 (View on PubMed)

Grindlay J, Babl FE. Review article: Efficacy and safety of methoxyflurane analgesia in the emergency department and prehospital setting. Emerg Med Australas. 2009 Feb;21(1):4-11. doi: 10.1111/j.1742-6723.2009.01153.x.

Reference Type BACKGROUND
PMID: 19254307 (View on PubMed)

Jacobs IG. Health effects of patients given methoxyflurane in the prehospital setting: a data linkage study. The Open Emergency Medicine Journal 3: 7-13, 2010.

Reference Type BACKGROUND

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.

Reference Type DERIVED
PMID: 32765053 (View on PubMed)

Mercadante S, Voza A, Serra S, Ruggiano G, Carpinteri G, Gangitano G, Intelligente F, Bonafede E, Sblendido A, Farina A, Soldi A, Fabbri A; MEDITA Study Group. Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA). Adv Ther. 2019 Nov;36(11):3030-3046. doi: 10.1007/s12325-019-01055-9. Epub 2019 Oct 12.

Reference Type DERIVED
PMID: 31612359 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30467809 (View on PubMed)

Related Links

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https://www.medicines.org.uk/emc/product/1939/smpc

Penthrox Summary of Product Characteristics

Other Identifiers

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MR311-3504

Identifier Type: -

Identifier Source: org_study_id

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