Clinical trial NCT03256903: Methoxyflurane vs Standard Analgesic Treatment for Trauma Pain in Spanish Emergency Units
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Pain Due to Trauma
Keywords: Methoxyflurane
emergency
trauma pain
inhaled analgesia
Lead sponsor: Mundipharma Pharmaceuticals S.L.
Sponsor class: INDUSTRY
Collaborators: name: Spanish Society for Emergency Medicine (SEMES)
name: Spanish Clinical Research Network - SCReN
First posted: 2017-08-22
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase IIIb open randomized clinical trial
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Pain relief
timeFrame: At baseline, 3, 5, 10, 15 and 20 minutes from STA
measure: Analgesia effectiveness
timeFrame: Change from baseline to 3, 5, 10, 15, 20 and 30 min
measure: Analgesia speed of action
timeFrame: From time of randomization up to 20 minutes
measure: Safety for patients with severe pain, treated with second or third step analgesics
timeFrame: Up until 14 days from STA
measure: Patient-averaged summed pain intensity difference 15 min after STA
timeFrame: from baseline to 3, 5, 10 and 15 minutes post dose
measure: Pain Responders
timeFrame: from baseline to 20 minutes post dose
Secondary outcomes:
measure: Investigators and patients satisfaction
timeFrame: 30 min from start of administration
measure: Patient and investigators' fulfillment of expectations
timeFrame: 30 min from start of administration
measure: Patients' Global Impression of Change with the treatments
timeFrame: Up until 30 minutes from STA
measure: Treatment cost of pain relief
timeFrame: Up until 60 minutes from randomization
measure: Safety rates of treatment emergent adverse events
timeFrame: Up until 14 days from STA
Other outcomes:
Locations:
city: Viladecans
country: Spain
facility: Hospital de Viladecans
state: Barcelona
city: Ponferrada
country: Spain
facility: Hospital del Bierzo
state: León
city: Coslada
country: Spain
facility: Hospital Asepeyo Coslada
state: Madrid
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
state: Pontevedra
city: Gernika-Lumo
country: Spain
facility: Hospital Gernika-Lumo
state: Vizcaya
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: SUMMA - Comunidad de Madrid
city: Madrid
country: Spain
facility: Hospital La Paz
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valladolid
country: Spain
facility: Hospital Campo Grande
city: Zamora
country: Spain
facility: Complejo Asistencial de Zamora
Study officials:
affiliation: La Paz University Hospital
name: Alberto Borobia, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.