Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA)

Fabbri, Andrea; Carpinteri, Giuseppe; Ruggiano, Germana; Bonafede, Elisabetta; Sblendido, Antonella; Farina, Alberto; Soldi, A

doi:10.1007/s12325-018-0830-x

Cited by 13 publications

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“…Study treatment was administered and all assessments were performed on the day of randomization, with a safety follow-up telephone call 14±2 days after discharge. The full methodology 25 and results for the full study population 21 have previously been reported.…”

Section: Methodsmentioning

confidence: 99%

“…The sample size calculation for the main study (including patients with both moderate and severe pain, assuming a non-inferiority margin of 1.0, a standard deviation of 2.5 and a significance level of 0.05 25 ) estimated that 108 patients per treatment group would provide 90% power to determine non-inferiority of methoxyflurane versus SAT for the change from baseline in VAS pain intensity over the first 10 min of treatment. Allowing for 20% of patients being non-evaluable, it was planned to randomize a total of 136 patients per treatment group.…”

Section: Sample Sizementioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

Section: Sample Sizementioning

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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“…conducted in UK emergency departments (EDs). 8 More recently, the MEDITA (Methoxyflurane in Emergency Department in Italy) trial [9][10][11] demonstrated superiority of methoxyflurane versus standard analgesic treatment (SAT), consisting of intravenous (IV) paracetamol or ketoprofen for moderate pain and IV morphine for severe pain, in terms of pain reduction up to 30 min after randomization, onset of pain relief, and satisfaction of healthcare professionals and patients. Subgroup analyses according to baseline pain (moderate, severe) showed that methoxyflurane was more effective than SAT in both cases.…”

Section: Introductionmentioning

confidence: 99%

Efficacy, Practicality, and Safety of Inhaled Methoxyflurane in Elderly Patients with Acute Trauma Pain: Subgroup Analysis of a Randomized, Controlled, Multicenter, Open-Label Trial (MEDITA)

Serra

Voza

Ruggiano

et al. 2020

JPR

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Acute trauma pain management in the elderly population is a challenge. Inhaled methoxyflurane represents a promising treatment option; however, data in the elderly population are limited. Patients and Methods: Subgroup, post hoc analysis including 69 patients aged ≥65 years from a randomized, active-controlled, open-label study in the emergency setting. Key inclusion criterion was moderate-to-severe pain (Numerical Rating Scale [NRS] score ≥ 4]) secondary to trauma in a single limb. Patients received inhaled methoxyflurane (3 mL) or standard analgesic treatment (SAT; IV paracetamol 1 g or ketoprofen 100 mg for moderate pain [NRS 4-6] and IV morphine 0.1mg/kg for severe pain [NRS ≥7]). The primary endpoint was the overall change in visual analog scale (VAS) pain intensity from randomization to the next 3, 5, and 10 min. Secondary endpoints included time to onset of pain relief (TOPR), efficacy up to 30 min, judgment of operators and patients, and safety. Results: Pain reduction over time was similar in both groups. Median TOPR was shorter for methoxyflurane (9 min; 95% CI: 7.8, 10.2 min) than SAT (15 min; 95% CI: 10.2, 19.8 min). In terms of treatment satisfaction, patients and operators rated treatment efficacy and practicality, respectively, as "Excellent" or "Very good" 5.7 times and 3.4 times more frequently than SAT. A similar rate of adverse events (methoxyflurane: 6 events; SAT: 7 events) was recorded, all nonserious. No clinically significant changes in vital signs parameters were observed, and methoxyflurane did not result in cases of bradycardia or hypotension. Conclusion: In elderly patients with trauma pain, inhaled methoxyflurane shows similar pain relief and safety compared to SAT, offering advantages in terms of onset of effect and user's satisfaction. Although this analysis presents some methodological limitations, it provides the first specific evidence of the use of inhaled methoxyflurane in the elderly population. Trial Registration: EudraCT number: 2017-001565-25; Clinicaltrials.gov identifier NCT03585374.

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“…We welcome the critical review by Montassier and Freund on our article on the rationale and methods of the “MEDITA” study [1]. Below, we provide point-by-point answers to all comments.…”

mentioning

confidence: 99%

“…Another ongoing study, “PenASAP”, will randomise 360 patients with trauma pain in a double-blind fashion to Penthrox or placebo, administered in addition to SoC [5]. These studies, together with the MEDITA study, which is the subject of this letter [1], all conducted with high methodological and qualitative standards, aim to resolve the uncertainties that currently persist.…”

mentioning

confidence: 99%

Response to “A Rigorous Evaluation of Methoxyflurane is Needed: Comment on ‘Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA)’”

et al. 2019

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Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA)

Cited by 13 publications

References 31 publications

<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>

<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>

<p>Efficacy, Practicality, and Safety of Inhaled Methoxyflurane in Elderly Patients with Acute Trauma Pain: Subgroup Analysis of a Randomized, Controlled, Multicenter, Open-Label Trial (MEDITA)</p>

Response to “A Rigorous Evaluation of Methoxyflurane is Needed: Comment on ‘Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA)’”

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