Prospective, Multicentre Trial of Methoxyflurane for Acute Trauma-Related Pain in Helicopter Emergency Medical Systems and Hostile Environments: METEORA Protocol

Marinangeli, Franco; Reggiardo, Giorgio; Sblendido, Antonella; Soldi, A; Farina, Alberto

doi:10.1007/s12325-018-0816-8

Cited by 10 publications

(11 citation statements)

References 35 publications

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“…Additional research on low-dose inhaled methoxyflurane could be useful to clearly establish its relative efficacy compared to opioids (including inhaled opioids) in patients with severe trauma pain, and in identifying the trauma patient profiles who could benefit the most from this acute pain treatment option. Finally, since METEORA 32 and METAMORPHOSIS studies are not yet complete, it is not possible to draw definitive conclusions on the use of methoxyflurane in hostile environments and on the organizational impact.…”

Section: Discussionmentioning

confidence: 99%

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Role of Inhaled Methoxyflurane in the Management of Acute Trauma Pain

Fabbri

Ruggiano

Collado

et al. 2020

JPR

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Adequate treatment of trauma pain is an integral part of the management of trauma patients, not just for ethical reasons but also because undertreated pain can lead to increased morbidities and worse long-term outcomes. Trauma pain management presents challenges in the pre-hospital setting, particularly in adverse or hostile environments as well as in busy emergency departments (EDs). Inhaled methoxyflurane, administered at analgesic doses via a disposable inhaler, has recently become available in Europe for the emergency treatment of moderate to severe pain in conscious adult trauma patients. A growing body of evidence demonstrates that inhaled methoxyflurane is well tolerated and effective in providing a rapid onset of analgesia. In this paper, we discuss the rationale for methoxyflurane use in trauma pain management, data from clinical trials recently conducted in Europe, its efficacy and safety profile compared to current standard treatments, its place in therapy and organizational impact. We conclude that inhaled methoxyflurane represents an effective treatment option in the different settings where trauma patients require rapid and flexible pain resolution, with potential organizational advantages.

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Section: Discussionmentioning

confidence: 99%

“…The primary endpoint of the METEORA study is the proportion of trauma patients who achieve at least 30% reduction in pain score on the VAS scale within 10 minutes from methoxyflurane inhalation. 32…”

Section: Penasap Study -Methoxyflurane As Part Of Multi-modal Analgesiamentioning

confidence: 99%

Role of Inhaled Methoxyflurane in the Management of Acute Trauma Pain

Fabbri

Ruggiano

Collado

et al. 2020

JPR

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“…Both studies showed high patient and healthcare professional (HCP) satisfaction with methoxyflurane treatment [18]. However, additional comparative studies versus the best currently available therapeutic options are needed to fully elucidate the place of methoxyflurane in emergency analgesia, including in extreme conditions such as helicopter rescue, which is the subject of an ongoing interventional study [27].…”

Section: Introductionmentioning

confidence: 99%

Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA)

et al. 2019

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IntroductionInhaled low-dose methoxyflurane is approved in Europe for emergency relief of moderate-to-severe trauma-related pain in adults, but data versus active comparators are sparse. The phase IIIb Methoxyflurane in Emergency Department in ITAly (MEDITA) trial investigated the analgesic efficacy, practicality and safety of methoxyflurane versus standard analgesic treatment (SAT) for acute trauma pain.MethodsThis was a randomised, active-controlled, parallel-group, open-label trial conducted in 15 Italian emergency units. Adults with limb trauma and pain score ≥ 4 on numerical rating scale (NRS) were randomised 1:1 to inhaled methoxyflurane 3 mL or SAT [intravenously administered (IV) morphine 0.1 mg/kg for severe pain (NRS ≥ 7); IV paracetamol 1 g or IV ketoprofen 100 mg for moderate pain (NRS 4–6)]. The primary endpoint was overall change in visual analogue scale (VAS) pain intensity from baseline (time of randomisation) to 3, 5 and 10 min. Non-inferiority and superiority of methoxyflurane versus SAT were concluded if the upper 95% confidence interval (CI) for the treatment comparison (methoxyflurane–SAT) was less than 1 and less than 0, respectively.ResultsBetween 8 February 2018 and 8 February 2019, 272 patients were randomised (136 per treatment group). A total of 270 patients (mean age 51 years; 49% male; 34% with severe pain; mean baseline VAS 67 mm) were treated and analysed for efficacy and safety. Superiority of methoxyflurane was demonstrated for moderate-to-severe pain (adjusted mean treatment difference − 5.94 mm; 95% CI − 8.83, − 3.06 mm), moderate pain (− 5.97 mm; 95% CI − 9.55, − 2.39 mm) and severe pain (− 5.54 mm; 95% CI − 10.49, − 0.59 mm). Median onset of pain relief was 9 min for methoxyflurane and 15 min for SAT. Practicality of methoxyflurane treatment was rated “Excellent”, “Very Good” or “Good” by 90% of clinicians vs. 64% for SAT. Adverse events (all non-serious) were reported by 17% of methoxyflurane-treated patients and 3% of SAT-treated patients.ConclusionMethoxyflurane provided superior pain relief to SAT in patients with moderate-to-severe trauma pain and may offer a simple, fast, effective non-opioid treatment option.Trial registrationTrial registered with EudraCT (2017-001565-25) on 2 March 2018 and ClinicalTrials.gov (NCT03585374) on 13 July 2018.FundingMundipharma Pharmaceuticals S.r.l.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01055-9) contains supplementary material, which is available to authorized users.

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“…Low-dose methoxyflurane analgesia has also been approved in Canada, Eastern Europe, Latin America, South Africa and the Gulf area. 18,19 Recently completed 20,21 and ongoing studies 22,23 have investigated the effectiveness of methoxyflurane analgesia versus currently used analgesic treatments in the emergency setting. The InMEDIATE trial in Spanish EDs compared methoxyflurane with standard analgesic treatment (SAT, administered according to local practice) and reported a significantly greater decrease in pain intensity (on the Numerical Rating Scale [NRS 0-10 ] over 20 min; 2.47 vs 1.39), faster onset of pain relief (3 vs 10 min) and better patient and HCP ratings of pain control and comfort of treatment with methoxyflurane treatment.…”

Section: Introductionmentioning

confidence: 99%

Inhaled Methoxyflurane versus Intravenous Morphine for Severe Trauma Pain in the Emergency Setting: Subgroup Analysis of MEDITA, a Multicenter, Randomized, Controlled, Open-Label Trial

Voza

Ruggiano

Serra

et al. 2020

JPR

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Opioid analgesics remain the cornerstone of treatment for severe trauma pain in the emergency setting, but there are barriers to their use. This post hoc analysis of a previously reported trial (MEDITA) investigated the efficacy and safety of low-dose methoxyflurane versus intravenous (IV) morphine for severe trauma pain. Patients and Methods: MEDITA was a Phase IIIb, randomized, active-controlled, parallelgroup, open-label study in Italian pre-hospital units and emergency departments (EudraCT: 2017-001565-25; NCT03585374). Adult patients (N=272) with moderate-to-severe trauma pain (score ≥4 on the Numerical Rating Scale [NRS]) were randomized 1:1 to inhaled methoxyflurane (3 mL) or standard analgesic treatment (SAT; IV paracetamol 1g or ketoprofen 100mg for moderate pain [NRS 4-6] and IV morphine 0.1mg/kg for severe pain [NRS ≥7]). Analyses were performed for the severe pain subgroup. The primary efficacy variable was the overall change from baseline in visual analog scale (VAS) pain intensity at 3, 5 and 10min post-randomization. Non-inferiority of methoxyflurane versus morphine was concluded if the upper 95% confidence interval (CI) for the treatment difference was <1; superiority was concluded if the upper 95% CI was <0. Results: Ninety-three patients (methoxyflurane: 49; SAT: 44) were included in the severe pain intention-to-treat population. The reduction in VAS pain intensity over the first 10min was superior for methoxyflurane versus morphine (adjusted mean treatment difference: −5.54mm; 95% CI: −10.49, −0.59mm; p=0.029). Median time to onset of pain relief was 9min for methoxyflurane and 15min for morphine. Patients rated treatment efficacy and physicians rated treatment practicality "Excellent" or "Very good" for more methoxyfluranetreated patients (42.8% and 67.3%) than morphine-treated patients (18.1% and 22.8%). Adverse events, all non-serious, were reported in 20.4% of methoxyflurane-treated patients and in 4.8% of morphine-treated patients. Conclusion: Methoxyflurane provided superior short-term pain relief to IV morphine in patients with severe trauma pain and offers an effective non-narcotic treatment option.

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Prospective, Multicentre Trial of Methoxyflurane for Acute Trauma-Related Pain in Helicopter Emergency Medical Systems and Hostile Environments: METEORA Protocol

Cited by 10 publications

References 35 publications

<p>Role of Inhaled Methoxyflurane in the Management of Acute Trauma Pain</p>

<p>Role of Inhaled Methoxyflurane in the Management of Acute Trauma Pain</p>

Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA)

<p>Inhaled Methoxyflurane versus Intravenous Morphine for Severe Trauma Pain in the Emergency Setting: Subgroup Analysis of MEDITA, a Multicenter, Randomized, Controlled, Open-Label Trial</p>

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