A comparison of three regimes with inhalational Methoxyflurane versus intranasal Fentanyl versus intravenous Morphine in prehospital acute pain management.

PreMeFen - PreMeFen

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-000549-42-NO

Enrollment

270

Registered

2021-03-19

Start date

2021-06-30

Completion date

Unknown

Last updated

2026-06-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Treatment of acute pain with Numeric Rating Scale (NRS) =4 in patients from 18 years of age carried out by ambulance workers in pre-hospital setting.

Interventions

Trade Name: PENTHROX 99.9% Product Name: PENTHROX 99.9% Pharmaceutical Form: Inhalation vapour, liquid Trade Name: Instanyl Product Name: Instanyl Pharmaceutical Form: Nasal spray, solution in single

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: >18 years of age Acute moderate to severe pain defined by self-reporting pain =4 on NRS Capable of giving informed consent Normal physiology defined by the following: Respiratory Rate/ minute =12 Heart rate/ minute 55-130 Oxygen saturation without supplementary oxygen =95 Systolic Blood Pressure (mmHg) =100 Glasgow Coma Score =14/15 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70

Exclusion criteria

Exclusion criteria: 1. Life-threatening or limb-threatening condition requiring immediate management 2. Pregnancy or breastfeeding 3. Know allergies, hypersensitivity or serious side effects to opioids or methoxyflurane or other excipients 4. Head injury or medical conditions with neurological impairment (GCS<14) 5. Previous malignant hyperthermia or persons with suspect genetic predisposition for malignant hyperthermia 6. Massive facial trauma, visible nasal blockage or on-going nose bleeding 7. History of severe liver disease with jaundice and scleral icterus 8. Dialysis or history of severe renal disease (known chronic kidney failure stage 4 or 5) 9. MAO-inhibitors last 14 days (pharmacological treatment of depression, Mb Parkinson or narcolepsy) 10. Myasthenia gravis 11. Use of IMP analgesics 12 hours prior to inclusion 12. Any condition that in the view of the study worker would suggest that the patient is unable to comply with study protocol and procedures.

Design outcomes

Primary

Measure	Time frame
Main Objective: Primary objective 1a To determine if a regimen of inhalation of 3 ml methoxyflurane is non-inferior to a regimen of intranasal 50 µ (>70) or 100 ug (>18, 18 years of age. (Repeated dosing allowed) Primary objective 1b: To determine if a regimen of inhalation of 3 ml methoxyflurane is non-inferior to a regimen of morphine IV 0.1 mg/kg (0.05 mg/kg from >70 years or fragile patients) in reduction of moderate to severe pain (NRS = 4) after 10 min, in patients >18 years of age. (Repeated dosing allowed) Primary objective 1c: To determine if a regimen of intranasal 50 µ(>70 years) or 100 ug (>18, 70 years old or fragile patients) in reduction of moderate to severe pain (NRS = 4) after 10 min, in patients >18 years of age. (Repeated dosing allowed) ;Secondary Objective: To assess the reduction in NRS from baseline at 5, 20, 30 minutes and/or to emergency department (ED) arrival To assess the need for rescue analgesia in the treatment groups To determine difference in time from scene arrival to IMP administration To determine time difference from scene arrival to pain reduction To determine any difference in level of sedation To determine any difference in change in respiratory rate (RR) To determine any difference in systolic blood pressure (SBP) To determine the level of overall health care personnel satisfaction of the treatment To determine the level of overall patient satisfaction of the treatment To determine differences in any adverse events or serious adverse events ;Primary end point(s): Changes in pain score NRS from time 0 to time 10 minutes ;Timepoint(s) of evaluation of this end point: Ten minutes after administration of IMP	—

Measure

Time frame

Main Objective: Primary objective 1a To determine if a regimen of inhalation of 3 ml methoxyflurane is non-inferior to a regimen of intranasal 50 µ (>70) or 100 ug (>18, 18 years of age. (Repeated dosing allowed) Primary objective 1b: To determine if a regimen of inhalation of 3 ml methoxyflurane is non-inferior to a regimen of morphine IV 0.1 mg/kg (0.05 mg/kg from >70 years or fragile patients) in reduction of moderate to severe pain (NRS = 4) after 10 min, in patients >18 years of age. (Repeated dosing allowed) Primary objective 1c: To determine if a regimen of intranasal 50 µ(>70 years) or 100 ug (>18, 70 years old or fragile patients) in reduction of moderate to severe pain (NRS = 4) after 10 min, in patients >18 years of age. (Repeated dosing allowed) ;Secondary Objective: *To assess the reduction in NRS from baseline at 5, 20, 30 minutes and/or to emergency department (ED) arrival *To assess the need for rescue analgesia in the treatment groups *To determine difference in time from scene arrival to IMP administration *To determine time difference from scene arrival to pain reduction *To determine any difference in level of sedation *To determine any difference in change in respiratory rate (RR) *To determine any difference in systolic blood pressure (SBP) *To determine the level of overall health care personnel satisfaction of the treatment *To determine the level of overall patient satisfaction of the treatment *To determine differences in any adverse events or serious adverse events ;Primary end point(s): Changes in pain score NRS from time 0 to time 10 minutes ;Timepoint(s) of evaluation of this end point: Ten minutes after administration of IMP

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Secondary

Measure	Time frame
Secondary end point(s): Change in pain score from t0-t5 Change in pain score from t0-t20 Change in pain score from t0-t30 Change in pain score from t0-tED-arrival Need for additional analgesia not in the regimen of the allocated treatment group: Difference in time arrival to administration of IMP Time from ambulance personnel arrival to first measure > 2 points reduction in NRS from baseline Change in level of sedation from t0 to T-10 and T-30 Change in RR t0 to T-10 and T-30 Change in SBP t0 to T-10 and T-30 Likert scale of HCP satisfaction at end of mission Likert scale of patient satisfaction at end of mission *Registration of AE and SAE during study period until end of intervention ;Timepoint(s) of evaluation of this end point: During ambulance mission	—

Measure

Time frame

Secondary end point(s): *Change in pain score from t0-t5 *Change in pain score from t0-t20 *Change in pain score from t0-t30 *Change in pain score from t0-tED-arrival *Need for additional analgesia not in the regimen of the allocated treatment group: *Difference in time arrival to administration of IMP *Time from ambulance personnel arrival to first measure > 2 points reduction in NRS from baseline *Change in level of sedation from t0 to T-10 and T-30 *Change in RR t0 to T-10 and T-30 *Change in SBP t0 to T-10 and T-30 *Likert scale of HCP satisfaction at end of mission *Likert scale of patient satisfaction at end of mission *Registration of AE and SAE during study period until end of intervention ;Timepoint(s) of evaluation of this end point: During ambulance mission

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Countries

Norway

Contacts

Public ContactAir Ambulance Department

Oslo University Hospital

frihey@ous-hf.no

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Jun 11, 2026