Use of the Methoxyflurane as Pain-killer in the Prehospital Management of Acute Myocardial Infarction (MAMI)

• Chest pain is the main symptom of acute myocardial infarction. A precocious analgesic treatment is justified by patient's comfort and unfavorable hemodynamic consequences of persistent pain. Morphine is the painkiller historically prescribed in this situation. Morphine has never been evaluated vs placebo and is strongly suspected to decrease oral anti-platelet efficacy. Then, morphine has been downgraded, in the 2017 European guidelines (European Society of Cardiology - ESC) from I to IIa. To find alternative treatment is required.
• The methoxyflurane is an anesthetic gas used in emergency setting for about twenty years. It is now commonly used in France. Its analgesic properties have been demonstrated. Its main advantages are its maneuverability as it is delivered by inhalation, i.e. without (before) any venous access and self-administered by the patient. Tolerability is good. It could be an excellent alternative to morphine.

Study Overview

• Status: Not yet recruiting
• Conditions: STEMI - ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Morphine; Drug: Methoxyflurane

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Frederic LAPOSTOLLE, MD,PHD; Phone Number: +33 01 48 96 44 54; Email: frederic.lapostolle@aphp.fr
• Study Contact Backup: Name: Frederic ADNET, MD,PHD; Phone Number: +33 01 48 96 44 54; Email: frederic.adnet@aphp.fr

Study Locations

• France
  • Bobigny, France, 93000
    • Hopital Avicenne
    • Contact: Frederic LAPOSTOLLE, MD PhD; Phone Number: +33 01 48 96 44 54; Email: frederic.lapostolle@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient age ≥ 18 years
• Patient managed in pre-hospital setting for a ST elevation myocardial infarction (STEMI) : Chest pain < 12 hours with moderate to severe pain (VAS > 6/10) or STEMI on ECG according to 2017 ESC guidelines

Exclusion Criteria:

• Previous analgesic treatment for this episode of chest pain
• Hypersensitivity to morphine, methoxyflurane, any fluorinated anesthetic or any of the excipients listed in SmPC,
• Decompensated respiratory failure (in the absence of artificial ventilation),
• Severe hepatocellular insufficiency (with encephalopathy),
• Acute head trauma and intracranial hypertension in the absence of controlled ventilation,
• Uncontrolled epilepsy,
• Treatment with buprenorphine, nalbuphine and pentazocine, naltrexone, nalmefene or sodium oxybate,
• Breastfeeding, in case of initiation or continuation after birth of a long-term treatment.
• Known malignant hyperthermia or genetic predisposition of the patient.
• History of serious adverse effects of the patient or his family after administration of inhaled anesthetics.
• History of signs of liver damage after use of methoxyflurane or after anesthesia with a halogenated hydrocarbon.
• Clinically significant renal impairment.
• Known renal failure with creatinine clearance below 30 ml/min or undergoing extracorporeal renal replacement therapy.
• Altered level of consciousness due to any cause, including head trauma, drug or alcohol use.
• Clinical evidence of cardiovascular instability (PAS <90 mm Hg).
• Clinical evidence of respiratory depression.
• Incapacity to self-assess pain intensity
• Incapacity to methoxyflurane self-administration
• Known pregnancy, breastfeeding, minors or incapacity (curatorship or guardianship)
• Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants
• Absence of a Social Security

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine; Morphine intra-venous infusion: 3 mg bolus repeated every 5 minutes until obtaining VAS ≤ 3	Drug: Morphine; Morphine intra-venous infusion: 3 mg bolus repeated every 5 minutes until obtaining VAS ≤ 3. Treatment: from inclusion to hospital arrival
Experimental: Methoxyflurane; Patient's self-administration of methoxyflurane (Penthrox®) with dedicated inhaler Initial dose: 3 mL (1 vial). A second 3 mL dose can be used.	Drug: Methoxyflurane; Patient's self-administration of methoxyflurane (Penthrox®) with dedicated inhaler Initial dose: 3 mL (1 vial). A second 3 mL dose can be used. Treatment: from inclusion to hospital arrival.; Other Names: Penthrox®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demonstrate that methoxyflurane self-administered by the patient is at least as efficient in achieving pain relief that morphine	To demonstrate that methoxyflurane self-administered by the patient suffering chest pain related to an acute myocardial infarction is at least as efficient in achieving pain relief that morphine with better tolerance (achieving pain relief, i.e. pain intensity score on visual analogic scale (VAS) ≤ 3 at 30 minutes)	at 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the impact of the treatments on heart rate	Impact of the treatments on cardiovascular system: heart rate (data collected every 5 minutes until to 30 minutes after randomisation and at hospital arrival)	at 30 minutes
Compare the impact of the treatments on arterial blood pressure	Impact of the treatments on cardiovascular system: arterial blood pressure (data collected every 5 minutes until to 30 minutes after randomisation and at hospital arrival)	at 30 minutes
Compare the impact of the treatments on pulse oximetry	Impact of the treatments on cardiovascular system: pulse oximetry (data collected every 5 minutes until to 30 minutes after randomisation and at hospital arrival)	at 30 minutes
Compare the impact of the treatments on ECG	Impact of the treatments on cardiovascular system: ECG changes before discharge from the ambulance	at 30 minutes
Compare tolerance of the treatments on respiratory depression	Tolerance of the treatments: respiratory depression: respiratory rate < 10 cycles per minutes (data collected every 5 minutes until to 30 minutes after randomisation and at hospital arrival)	at 30 minutes
Compare tolerance of the treatments on sedation	Tolerance of the treatments: sedation: Richmond Agitation Sedation Scale (RASS) ≥ 2 or ≤ -2 (data collected every 5 minutes until to 30 minutes after randomisation and at hospital arrival)	at 30 minutes
Compare tolerance of the treatments on dizziness, pruritus, nausea, vomiting, headache	Tolerance of the treatments: dizziness, pruritus, nausea, vomiting, headache (data collected every 5 minutes until to 30 minutes after randomisation and at hospital arrival)	at 30 minutes
Compare the impact of the treatments on pain relief	Time before achieving pain relief, i.e. time to reach initial pain divided by two (initial VAS / 2)	From randomization until the first documented pain divided by two, assessed up to 30 minutes
Compare the impact of the treatments on pain relief	Time before achieving pain relief, i.e. time between randomisation and pain intensity score on VAS ≤ 3	From randomization until the first documented pain relief, assessed up to 30 minutes

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Medical Developments International Limited

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: chest pain; morphine; methoxyflurane
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; ST Elevation Myocardial Infarction; Chest Pain; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Ethers; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Methyl Ethers; Ethyl Ethers; Morphine; Methoxyflurane
• Other Study ID Numbers: APHP180610; 2025-523349-86-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No