E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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.
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E.1.1.1 | Medical condition in easily understood language |
Acute pain treated by ambulance personnel outside of hospital |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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, <70 years) fentanyl in reduction of moderate to severe pain (NRS ≥ 4) after 10 min in patients >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) fentanyl is non-inferior to a regimen of morphine IV 0.1 mg/kg (or 0.05 mg/kg >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)
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E.2.2 | Secondary objectives of the trial |
*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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in pain score NRS from time 0 to time 10 minutes |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Ten minutes after administration of IMP |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |