Acute Traumatic PainPhase 3MEDITANCT03585374
Trauma Acute Pain Treatment With Methoxyflurane Vaporized (PENTHROX®): Efficacy and Safety Study (MEDITA)
A Phase 3 study testing Methoxyflurane and Penthrox inhaler, Morphine and Paracetamol in people with Acute Traumatic Pain, run by Mundipharma Pharmaceuticals srl at 16 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Traumatic Pain
- What is being tested?
- Methoxyflurane and Penthrox inhaler, Morphine and Paracetamol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 272 participants
- Where
- 16 sitesItaly
- Study dates
- 8 Feb 2018to 22 Feb 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 25Show fewer
- 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 locations and contacts
16 sites in 1 country.
16 sites in 1 country
Italy16 sites
Azienda Sanitaria di Firenze Ospedale Santa Maria Annunziata DEA -Medicina D'Urgenza
Bagno a Ripoli, FI, 50126
AO Universitaria- Policlinico V.Emanuele Medicina e Chirurgia d'Accettazione e d'Urgenza
Catania, CT, 95123
AO per l'Emergenza- Cannizzaro UO Servizio di Urgenza Emergenza Sanitaria 118
Catania, CT, 95126
Medicina D'Urgenza ed Accettazione Azienda Ospedaliera di Catanzaro "Pugliese-Ciaccio"
Catanzaro, CZ, 88100
AUSL della ROMAGNA Ospedale M. Bufalini Pronto Soccorso - Medicina d'Urgenza
Cesena, Forlì-Cesena, 47522
OSPEDALE DI FAENZA Pronto Soccorso - Medicina d'Urgenza
Faenza, Ravenna, 48018
Azienda USL della Romagna - Forlì Unità Operativa Pronto Soccorso, Medicina d'Urgenza, 118
Forlì, FC, 47121
IRCCS San Martino Servizio 118
Genova, GE, 16132
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Dipartimento di Anestesia e Terapia Intensiva Donna-Bambino
Milan, MI, 20122
ULSS 6 EUGANEA ex Ulss 16 Pronto Soccorso e Medicina d'Urgenza Ospedale S. Antonio
Padova, PD, 35127
Azienda USL Toscana Centro U.O. Centrale Operativa 118
Pistoia, 51100
AUSL della ROMAGNA Ospedale degli Infermi U.O. Pronto Soccorso - Medicina d'Urgenza
Rimini, 47923
Istituto Clinico Humanitas - Pneumologia e Medicina d'urgenza
Rozzano, Milan, 20089
AOU (Azienda Ospedaliera Universitaria) Sassari Unità Operativa Complessa Medicina d'Accettazione e d'Urgenza - P.S. - O.B.I.
Sassari, SS, 07100
ATS (Azienda tutela Salute)_Struttura Complessa Centrale Operativa 118
Sassari, SS, 07100
Medicina e Chirurgia di accettazione e di urgenza Humanitas Gradenigo - Presidio Sanitario
Torino, TO, 10153
About this study
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
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.
- Conditions
- Acute Traumatic Pain
- Being tested
- Methoxyflurane and Penthrox inhaler, Morphine, Paracetamol, Ketoprofen
- Keywords
- pain, methoxyflurane, Penthrox
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methoxyflurane and Penthrox inhalerCombination product
Also called Penthrox
3ml of methoxyflurane vaporized through an inhaler (Penthrox). Inhalation, by regular breathing, last about 25 minutes.
MorphineDrug
Also called Morphine for intravenous use
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.
ParacetamolDrug
Also called Paracetamol for intravenous use
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.
KetoprofenDrug
Also called Ketoprofen for intravenous use
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.
| Study group | Role | What they receive |
|---|---|---|
| A_test drug_Methoxyflurane (Penthrox®) | Experimental | 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. Receives: Combination Product: Methoxyflurane and Penthrox inhaler |
| B_comparator_Morphine/Paracetamol/Ketoprofen | Active comparator | 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. Receives: Drug: Morphine; Drug: Paracetamol; Drug: Ketoprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline up to 10 minutes later.
Secondary outcomes (13)
Need for rescue medication.
Percentage of patients who are using rescue medication for insufficient or unsatisfactory therapeutic effect of the trial drugs.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From baseline up to 30 minutes later or to the end of the treatment (whichever occurs first).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2018
- Study start8 Feb 2018
- Primary completion8 Feb 2019
- Study completion22 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Acute Traumatic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 272 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mundipharma Pharmaceuticals srl
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bioikos Ambiente Srl
- Responsible party
- Sponsor
- Investigators
- Germana Ruggiano, Dr, Principal investigator, Azienda Sanitaria di Firenze Ospedale Santa Maria Annunziata DEA -Medicina D'Urgenza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03585374
- Sponsor's protocol ID
- MR311-3504
- Acronym
- MEDITA
- Status last verified
- Dec 2018
- First submitted
- 31 May 2018
- Last updated
- 9 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 17306626Guru 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.
PubMed 10645828Brown 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.
PubMed 12883507Rupp 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.
PubMed 15039693Berben 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.
PubMed 21505324Dale 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.
PubMed 26514633Mills 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.
PubMed 19549018Pines 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.
PubMed 17913299Dayan 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.
PubMed 25926525Tomi 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.
PubMed 8329263Coffey 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.
PubMed 24743584Grindlay 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.
PubMed 19254307Jacobs IG. Health effects of patients given methoxyflurane in the prehospital setting: a data linkage study. The Open Emergency Medicine Journal 3: 7-13, 2010.
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.
PubMed 32765053Mercadante 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.
PubMed 31612359
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03585374
- Acronym / sponsor ID
- MEDITA / MR311-3504
- Conditions
- Acute Traumatic Pain
- Keywords
- pain, methoxyflurane, Penthrox
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 272 participants (actual)
- Lead sponsor
- Mundipharma Pharmaceuticals srlIndustry (pharma, biotech, devices)
- Collaborators
- Bioikos Ambiente Srl
- Study start
- 8 Feb 2018 (actual)
- Primary completion
- 8 Feb 2019 (actual)
- Study completion
- 22 Feb 2019 (actual)
- First posted
- 13 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| A_test drug_Methoxyflurane (Penthrox®) | Experimental | Combination Product: Methoxyflurane and Penthrox inhalerPain 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. |
| B_comparator_Morphine/Paracetamol/Ketoprofen | Active comparator | Drug: Morphine, Drug: Paracetamol, Drug: KetoprofenThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (25 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methoxyflurane and Penthrox inhalerAlso: Penthrox3ml of methoxyflurane vaporized through an inhaler (Penthrox). Inhalation, by regular breathing, last about 25 minutes. | Combination product | A_test drug_Methoxyflurane (Penthrox®) |
| MorphineAlso: Morphine for intravenous useEach 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. | Drug | B_comparator_Morphine/Paracetamol/Ketoprofen |
| ParacetamolAlso: Paracetamol for intravenous useEach 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. | Drug | B_comparator_Morphine/Paracetamol/Ketoprofen |
| KetoprofenAlso: Ketoprofen for intravenous useEach 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. | Drug | B_comparator_Morphine/Paracetamol/Ketoprofen |
Primary outcome
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.
13 secondary outcomes
Need for rescue medication.
Time frame: From baseline up to 30 minutes later.
Change in the intensity of pain within 30 minutes.
Time frame: From baseline up to 30 minutes later.
Time to pain relief.
Time frame: From baseline up to 30 minutes.
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).
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).
Need for dilution hole closure (only Experimental Arm).
Time frame: From baseline up to 30 minutes later.
Change in the intensity of pain within 30 minutes by trauma type.
Time frame: From baseline up to 30 minutes later.
Incidence of Treatment-Emergent Adverse Events (AE)
Time frame: From baseline up to 16 days later.
Change in pulse rate
Time frame: From baseline up to 30 minutes later.
Change in blood pressure
Time frame: From baseline up to 30 minutes later.
Change in respiration rate
Time frame: From baseline up to 30 minutes later.
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.
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2019.
- Background: PubMed 17306626Todd 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.
- Background: PubMed 10645828Guru 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.
- Background: PubMed 12883507Brown 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.
- Background: PubMed 15039693Rupp 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.
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- Penthrox Summary of Product CharacteristicsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Germana Ruggiano, Dr principal investigator
Azienda Sanitaria di Firenze Ospedale Santa Maria Annunziata DEA -Medicina D'Urgenza
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methoxyflurane and Penthrox inhaler, Morphine and Paracetamol in people with Acute Traumatic Pain, run by Mundipharma Pharmaceuticals srl at 16 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the intensity of pain within 10 minutes. (time frame: From baseline up to 10 minutes later.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03585374, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2019.