Acute Pain Due to TraumaPhase 3InMEDIATENCT03256903
Methoxyflurane vs Standard Analgesic Treatment for Trauma Pain in Spanish Emergency Units
A Phase 3 study testing Methoxyflurane in people with Acute Pain Due to Trauma, run by Mundipharma Pharmaceuticals S.L. at 14 sites in Spain.
Trial summary
Clinical trial to compare pain relief between methoxyflurane and any analgesic treatment used in usual clinical practice, in patients with trauma and associated pain, treated in Spanish emergency units. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Pain Due to Trauma
- What is being tested?
- Methoxyflurane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 310 participants
- Where
- 14 sitesSpain
- Study dates
- 7 Jul 2017to 31 Jul 2018
- 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
- Adult patients: ≥ 18 years of age
- Moderate to severe pain (NRS 0-10; >=4) secondary to trauma
- Without anticipating surgery due to the trauma, requiring hospitalization (hospital stay 12h)
- Conscious patient.
- Giving informed consent in writing
Who cannot join
- Hypersensitivity to methoxyflurane (MEOF) or any fluorinated anaesthetic.
- Malignant hyperthermia: patients with known or genetically susceptible to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives.
- Patients who have a history of showing signs of liver damage after previous MEOF use or halogenated hydrocarbon anaesthesia
- Known clinically significant renal impairment
- Known pregnant or likely to be pregnant women at the time of inclusion.
- Clinically evident cardiovascular instability
Show all 12Show fewer
- Clinically evident respiratory depression
- Patients taken any analgesic for the traumatic pain before inclusion
- Altered level of consciousness due to any cause, including head injury, drugs or alcohol
- Degenerative diseases, mental illness or other conditions that could affect ability of valuing pain intensity
- Patients to be unable to understand the purpose of the study and perform self-assessments, following investigator's criteria.
- Participation in another clinical trial within 30 days prior to randomization
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Spain14 sites
Hospital General de Alicante
Alicante, 03010
Hospital Asepeyo Coslada
Coslada, Madrid, 28823
Hospital Gernika-Lumo
Gernika-Lumo, Vizcaya, 48300
Hospital Universitario La Princesa
Madrid, 28006
Hospital Clínico San Carlos
Madrid, 28040
SUMMA - Comunidad de Madrid
Madrid, 28045
Hospital La Paz
Madrid, 28046
Hospital Puerta de Hierro
Majadahonda, Madrid, 28222
Hospital del Bierzo
Ponferrada, León, 24404
Hospital Virgen del Rocío
Seville, 41013
Hospital Campo Grande
Valladolid, 47006
Hospital Álvaro Cunqueiro
Vigo, Pontevedra, 36312
Hospital de Viladecans
Viladecans, Barcelona, 08840
Complejo Asistencial de Zamora
Zamora, 49022
About this study
Official title: Open Randomized Clinical Trial to Compare Pain Relief Between Methoxyflurane and Standard of Care for Treating Patients With Trauma Pain in Spanish Emergency Units.
Clinical trial to compare pain relief between methoxyflurane and any analgesic treatment used in usual clinical practice, in patients with trauma and associated pain, treated in Spanish emergency units.
Read the detailed description
Open, randomized clinical trial to compare emergency pain relief between methoxyflurane and standard of care in patients with trauma and associated pain, treated in Spanish emergency units.
Methoxyflurane is a fluorinated ethyl methyl ether, with the chemical name 2:2-dichloro-1:1-difluoroethyl methyl ether. It belongs to the fluorinated hydrocarbon group of volatile anaesthetics. It is inhaled as a vapour at low (sub-anaesthetic) concentrations to achieve an analgesic effect for the management of pain.
In Europe countries, where methoxyflurane is already marketed, it is indicated for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain.
On the other hand, current clinical practice includes a variety of analgesic agents, with the choice of which to employ based on consideration of the risk-benefit factors of each class of drug, as well as the type of pain, its severity, and the risk of adverse effects.
The main objective of this study is to assess Methoxyflurane's significant advantage in terms of anaglesic effectiveness, as it is known as a rapidly acting, non-narcotic analgesic for the treatment of emergency pain.
- Conditions
- Acute Pain Due to Trauma
- Being tested
- Methoxyflurane, Standard of care
- Keywords
- Methoxyflurane, emergency, trauma pain, inhaled analgesia
- Medical subject headings
- Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethoxyfluraneDrug
Also called No other interventions
Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.
Standard of careDrug
Also called No other interventions
Any kind of analgesia, administered by any route for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain
| Study group | Role | What they receive |
|---|---|---|
| Methoxyflurane | Experimental | Patients will be supplied with up to two inhalers containing 3 mL methoxyflurane. A member of the research team will train the patient to self-administer methoxyflurane Receives: Drug: Methoxyflurane |
| Standard of Care (SoC) | Active comparator | Patients will be treated following standard of care (SoC) of the hospital, for emergency relief of trauma and associated pain. Any kind of analgesia administered by any route will be valid. Only administration of one analgesic (or fixed combinations) at baseline will considered SoC. Other required analgesics will be considered rescue medication. Receives: Drug: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain relief
Change in mean pain intensity over 20 min from start of administration (STA) and time to first pain relief, measured by numeric scale (0-10)
Measured: At baseline, 3, 5, 10, 15 and 20 minutes from STA
Analgesia effectiveness
Difference between arms related to analgesia effectiveness
Measured: Change from baseline to 3, 5, 10, 15, 20 and 30 min
Analgesia speed of action
Difference between arms related to speed of action of analgesia for all patients
Measured: From time of randomization up to 20 minutes
Safety for patients with severe pain, treated with second or third step analgesics
Difference between arms related to safety for patients with severe pain (NRS >7), treated with second or third step analgesics
Measured: Up until 14 days from STA
Patient-averaged summed pain intensity difference 15 min after STA
Patient-averaged summed pain intensity difference 15 min after STA
Measured: from baseline to 3, 5, 10 and 15 minutes post dose
Pain Responders
Pain Responders (with >30% pain relief compared to baseline) at 20 min
Measured: from baseline to 20 minutes post dose
Secondary outcomes (5)
Investigators and patients satisfaction
Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)
Measured: 30 min from start of administration
Patient and investigators' fulfillment of expectations
Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale
Measured: 30 min from start of administration
Patients' Global Impression of Change with the treatments
Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale
Measured: Up until 30 minutes from STA
Treatment cost of pain relief
Treatment cost of pain relief, measured considering use of fungible material; need of nurse to administer iv treatments; time to discharge
Measured: Up until 60 minutes from randomization
Safety rates of treatment emergent adverse events
Safety rates of treatment emergent adverse events (TEAE) in both arms, including alterations in biochemical and blood count.
Measured: Up until 14 days from STA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start7 Jul 2017
- Primary completion6 Mar 2018
- Study completion31 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Pain Due to TraumaStudies 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
- Phase IIIb open randomized clinical trial
- Masking
- None (open label)
- Enrolment
- 310 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mundipharma Pharmaceuticals S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Spanish Society for Emergency Medicine (SEMES), Spanish Clinical Research Network - SCReN
- Responsible party
- Principal investigator, Alberto M. Borobia, Hospital Universitario La Paz
- Investigators
- Alberto Borobia, MD, PhD, Study director, La Paz University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03256903
- Sponsor's protocol ID
- MR311-3502
- Acronym
- InMEDIATE
- Status last verified
- Aug 2018
- First submitted
- 30 May 2017
- Last updated
- 20 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Borobia AM, Collado SG, Cardona CC, Pueyo RC, Alonso CF, Torres IP, Gonzalez MC, Casal Codesido JR, Betegon MA, Barcela LA, Andicoechea AO, Testa AF, Colina JT, Dorribo AC, Del Arco Galan C, Martinez Avila JC, Lugilde ST, Carcas Sansuan AJ; InMEDIATE Investigators Group. Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments. Ann Emerg Med. 2020 Mar;75(3):315-328. doi: 10.1016/j.annemergmed.2019.07.028. Epub 2019 Oct 14.
PubMed 31623936
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Randomized Clinical Trial to Compare Pain Relief Between Methoxyflurane and Standard of Care for Treating Patients With Trauma Pain in Spanish Emergency Units.
- ClinicalTrials.gov ID
- NCT03256903
- Acronym / sponsor ID
- InMEDIATE / MR311-3502
- Conditions
- Acute Pain Due to Trauma
- Keywords
- Methoxyflurane, emergency, trauma pain, inhaled analgesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 310 participants (actual)
- Lead sponsor
- Mundipharma Pharmaceuticals S.L.Industry (pharma, biotech, devices)
- Collaborators
- Spanish Society for Emergency Medicine (SEMES), Spanish Clinical Research Network - SCReN
- Study start
- 7 Jul 2017 (actual)
- Primary completion
- 6 Mar 2018 (actual)
- Study completion
- 31 Jul 2018 (actual)
- First posted
- 22 Aug 2017 (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.
Clinical trial to compare pain relief between methoxyflurane and any analgesic treatment used in usual clinical practice, in patients with trauma and associated pain, treated in Spanish emergency units.
Detailed description
Open, randomized clinical trial to compare emergency pain relief between methoxyflurane and standard of care in patients with trauma and associated pain, treated in Spanish emergency units.
Methoxyflurane is a fluorinated ethyl methyl ether, with the chemical name 2:2-dichloro-1:1-difluoroethyl methyl ether. It belongs to the fluorinated hydrocarbon group of volatile anaesthetics. It is inhaled as a vapour at low (sub-anaesthetic) concentrations to achieve an analgesic effect for the management of pain.
In Europe countries, where methoxyflurane is already marketed, it is indicated for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain.
On the other hand, current clinical practice includes a variety of analgesic agents, with the choice of which to employ based on consideration of the risk-benefit factors of each class of drug, as well as the type of pain, its severity, and the risk of adverse effects.
The main objective of this study is to assess Methoxyflurane's significant advantage in terms of anaglesic effectiveness, as it is known as a rapidly acting, non-narcotic analgesic for the treatment of emergency pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase IIIb open randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Methoxyflurane | Experimental | Drug: MethoxyfluranePatients will be supplied with up to two inhalers containing 3 mL methoxyflurane. A member of the research team will train the patient to self-administer methoxyflurane |
| Standard of Care (SoC) | Active comparator | Drug: Standard of carePatients will be treated following standard of care (SoC) of the hospital, for emergency relief of trauma and associated pain. Any kind of analgesia administered by any route will be valid. Only administration of one analgesic (or fixed combinations) at baseline will considered SoC. Other required analgesics will be considered rescue medication. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients: ≥ 18 years of age
- Moderate to severe pain (NRS 0-10; >=4) secondary to trauma
- Without anticipating surgery due to the trauma, requiring hospitalization (hospital stay 12h)
- Conscious patient.
- Giving informed consent in writing
Key exclusion criteria (12 listed)
- Hypersensitivity to methoxyflurane (MEOF) or any fluorinated anaesthetic.
- Malignant hyperthermia: patients with known or genetically susceptible to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives.
- Patients who have a history of showing signs of liver damage after previous MEOF use or halogenated hydrocarbon anaesthesia
- Known clinically significant renal impairment
- Known pregnant or likely to be pregnant women at the time of inclusion.
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 |
|---|---|---|
| MethoxyfluraneAlso: No other interventionsUp to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day. | Drug | Methoxyflurane |
| Standard of careAlso: No other interventionsAny kind of analgesia, administered by any route for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain | Drug | Standard of Care (SoC) |
Primary outcome
Pain relief
Time frame: At baseline, 3, 5, 10, 15 and 20 minutes from STA
Change in mean pain intensity over 20 min from start of administration (STA) and time to first pain relief, measured by numeric scale (0-10)
Analgesia effectiveness
Time frame: Change from baseline to 3, 5, 10, 15, 20 and 30 min
Difference between arms related to analgesia effectiveness
Analgesia speed of action
Time frame: From time of randomization up to 20 minutes
Difference between arms related to speed of action of analgesia for all patients
Safety for patients with severe pain, treated with second or third step analgesics
Time frame: Up until 14 days from STA
Difference between arms related to safety for patients with severe pain (NRS >7), treated with second or third step analgesics
Patient-averaged summed pain intensity difference 15 min after STA
Time frame: from baseline to 3, 5, 10 and 15 minutes post dose
Patient-averaged summed pain intensity difference 15 min after STA
Pain Responders
Time frame: from baseline to 20 minutes post dose
Pain Responders (with >30% pain relief compared to baseline) at 20 min
5 secondary outcomes
Investigators and patients satisfaction
Time frame: 30 min from start of administration
Patient and investigators' fulfillment of expectations
Time frame: 30 min from start of administration
Patients' Global Impression of Change with the treatments
Time frame: Up until 30 minutes from STA
Treatment cost of pain relief
Time frame: Up until 60 minutes from randomization
Safety rates of treatment emergent adverse events
Time frame: Up until 14 days from STA
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 20 Aug 2018.
- Derived from this study: PubMed 31623936Borobia AM, Collado SG, Cardona CC, Pueyo RC, Alonso CF, Torres IP, Gonzalez MC, Casal Codesido JR, Betegon MA, Barcela LA, Andicoechea AO, Testa AF, Colina JT, Dorribo AC, Del Arco Galan C, Martinez Avila JC, Lugilde ST, Carcas Sansuan AJ; InMEDIATE Investigators Group. Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments. Ann Emerg Med. 2020 Mar;75(3):315-328. doi: 10.1016/j.annemergmed.2019.07.028. Epub 2019 Oct 14.
- Individual participant dataSharing planned: Undecided
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.
Alberto Borobia, MD, PhD study director
La Paz University Hospital
14 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 in people with Acute Pain Due to Trauma, run by Mundipharma Pharmaceuticals S.L. at 14 sites in Spain.
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 5 inclusion and 12 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 20 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Spain. 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?
Pain relief (time frame: At baseline, 3, 5, 10, 15 and 20 minutes from STA). The study lists 6 primary outcomes in all. 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 NCT03256903, which also lists 1 linked publication.
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 20 Aug 2018.