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

Figures & data

Table 1 Patient Characteristics (Severe Pain Subgroup, ITT Population)

Characteristic		Methoxyflurane (N=49)	Standard Analgesic Treatment (IV Morphine) (N=44)
Age (years)	Mean (SD)	53.1 (18.42)	57.4 (19.34)
	Range	19-91	19–95
Gender [n (%)]	Male	20 (40.8)	15 (34.1)
	Female	29 (59.2)	29 (65.9)
Race [n (%)]	Caucasian	46 (93.9)	43 (97.7)
	Asian	1 (2.0)	0
	Black	2 (4.1)	1 (2.3)
NRS Score at Inclusion [n (%)]	7	13 (26.5)	9 (20.5)
	8	16 (32.7)	25 (56.8)
	9	15 (30.6)	6 (13.6)
	10	5 (10.2)	4 (9.1)
VAS baseline score (mm)	Mean (SD)	81 (15)	79 (14)

Abbreviations: ITT, intention-to-treat; NRS, Numerical Rating Scale; SD, standard deviation; VAS, visual analog scale.

Figure 1 Participant flow (severe pain subgroup).

Abbreviations: ITT, intention-to-treat; IV, intravenous; SAT, standard analgesic treatment.

Table 2 Analysis of Change from Baseline in VAS Pain Intensity (Severe Pain Subgroup, ITT Population)

Endpoint	Time Point (min)	Mean Change from Baseline (95% Confidence Interval)^a		Estimated Treatment Effect (95% Confidence Interval)	p-value
		Methoxyflurane	Standard Analgesic Treatment
Primary Endpoint	3	−4.69 (−7.27, −2.11)	−0.96 (−3.68, 1.76)	−3.73 (−7.48, 0.02)	0.051
	5	−14.89 (−18.80, −10.99)	−6.26 (−10.38, −2.13)	−8.64 (−14.32, −2.96)	0.003^b
	10	−21.87 (−26.93, −16.81)	−17.62 (−22.96, −12.28)	−4.25 (−11.61, 3.11)	0.254
	Overall	−13.82 (−17.22, −10.42)	−8.28 (−11.87, −4.69)	−5.54 (−10.48, −0.59)	0.029^b
Secondary Endpoint	15	−27.25 (22.23)	−26.81 (17.92)	−0.44 (−8.86, 7.98)	0.917
	20	−33.43 (22.49)	−31.45 (20.05)	−1.98 (−11.04, 7.08)	0.665
	25	−38.41 (23.34)	−38.85 (19.16)	0.44 (−8.73, 9.61)	0.924
	30	−43.96 (23.42)	−43.88 (18.96)	−0.08 (−9.23, 9.08)	0.986

Notes: Based on estimated marginal means. ^aMean change from baseline (standard deviation) is presented for 15, 20, 25 and 30 min time points. ^bMean difference significant at the 0.05 level (Bonferroni adjustment for multiple comparisons).

Abbreviations: ITT, intention-to-treat; VAS, visual analog scale.

Figure 2 Change from baseline in VAS pain intensity (severe pain subgroup, ITT population). Mean change ± standard error.

Abbreviations: ITT, intention-to-treat; SAT, standard analgesic treatment.

Figure 3 VAS responder rate (severe pain subgroup, ITT population). VAS responder: patient with ≥30% reduction from baseline in VAS pain intensity.

Abbreviations: ITT, intention-to-treat; SAT, standard analgesic treatment; VAS, visual analog scale.

Figure 4 Kaplan-Meier plot of time to onset of pain relief (severe pain subgroup, ITT population). The Kaplan-Meier curve represents an estimate of the cumulative proportion of patients who have not yet experienced onset of pain relief. Higher curves indicate longer time to pain relief. No censoring was performed.

Figure 5 Patient and physician-reported outcomes (severe pain subgroup, ITT population). (A) Overall treatment efficacy evaluated by the patient. (B) Practicality of using study treatment evaluated by the physician.

Table 3 Adverse Events (Severe Pain Subgroup, Safety Population)

Number (%) of Patients	Methoxyflurane (N=49)	IV Morphine (N=42)
Any adverse event	10 (20.4)	2 (4.8)
Nausea	2 (4.1)	0
Feeling abnormal	2 (4.1)	0
Dysgeusia	2 (4.1)	0
Vertigo	1 (2.0)	0
Oral discomfort	1 (2.0)	0
Feeling drunk	1 (2.0)	0
Pyrexia	1 (2.0)	0
Bronchitis	1 (2.0)	0
Presyncope	1 (2.0)	0
Sedation	1 (2.0)	0
Euphoric mood	1 (2.0)	0
Vomiting	0	1 (2.4)
Pruritus	0	1 (2.4)

Notes: AEs are presented by MedDRA preferred term in decreasing order of frequency in the methoxyflurane group, followed by the standard analgesic treatment (IV morphine) group. 

Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; IV, intravenous.