Methoxyflurane vs Standard Analgesic Treatment for Trauma Pain in Spanish Emergency Units

Study Overview
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Brief Summary
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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
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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.

Official Title
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Open Randomized Clinical Trial to Compare Pain Relief Between Methoxyflurane and Standard of Care for Treating Patients With Trauma Pain in Spanish Emergency Units.

Conditions
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Acute Pain Due to Trauma

Intervention / Treatment
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* Drug: Methoxyflurane
* Drug: Standard of care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase IIIb open randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methoxyflurane<br>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 | Drug: Methoxyflurane<br>* Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.<br>* Other names: No other interventions;|
| Active Comparator: Standard of Care (SoC)<br>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. | Drug: Standard of care<br>* 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<br>* Other names: No other interventions;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | At baseline, 3, 5, 10, 15 and 20 minutes from STA | 
| Analgesia effectiveness | Difference between arms related to analgesia effectiveness | 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 | 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 | 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 | 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 | from baseline to 20 minutes post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigators and patients satisfaction | Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10) | 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 | 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 | 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 | 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. | Up until 14 days from STA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methoxyflurane, emergency, trauma pain, inhaled analgesia