title: STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain.
abstract: OBJECTIVE
  To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma.
  
  
  METHODS
  STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12-17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses.
  
  
  RESULTS
  A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of -18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action.
  
  
  CONCLUSIONS
  The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic.
  
  
  BACKGROUND
  NCT01420159.
authors.affiliation: DREEAM: Department of Research and Education in Emergency Medicine, Acute Medicine and Major Trauma, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Coffey
authors.affiliation: Emergency Department, Royal Victoria Infirmary, Newcastle Upon Tyne, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.affiliation: Emergency Department, Birmingham Children's Hospital, Birmingham, West Midlands, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Hartshorn
authors.affiliation: Emergency Department, James Cook University Hospital, Middlesbrough, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Hunt
authors.affiliation: Emergency Department, Barnsley District General Hospital, Barnsley, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Locker
authors.affiliation: Accident and Emergency Department, Colchester Hospital University Foundation NHS Trust, Colchester, UK.
authors.forename: Kazim
authors.initials: K
authors.lastname: Mirza
authors.affiliation: Emergency Department, James Cook University Hospital, Middlesbrough, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dissmann
mesh_terms: D059787:Acute Pain / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000698:Analgesia / Q000379:methods*; D018685:Anesthetics, Inhalation / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008733:Methoxyflurane / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects / Q000706:statistics & numerical data; D006113:United Kingdom; D055815:Young Adult
chemical_list: D018685:Anesthetics, Inhalation; D008733:Methoxyflurane
keywords: Analgesia/Pain Control; Emergency Department; Research, Clinical
references.citation: Postgrad Med J. 1972 Mar;48(557):128-32
references.pmid: 5024149
references.citation: Int Anesthesiol Clin. 1974 Summer;12(2):93-105
references.pmid: 4603054
references.citation: Br J Anaesth. 1973 Jul;45(7):719-25
references.pmid: 4730164
references.citation: Emerg Med J. 2011 Jan;28(1):57-63
references.pmid: 20466829
references.citation: Anesthesiology. 1966 Sep-Oct;27(5):591-607
references.pmid: 5918999
references.citation: Can Anaesth Soc J. 1970 May;17(3):275-8
references.pmid: 5512851
references.citation: Pain. 2001 Nov;94(2):149-158
references.pmid: 11690728
references.citation: Br J Anaesth. 1993 Jun;70(6):684-6
references.pmid: 8329263
references.citation: Can Anaesth Soc J. 1969 Jan;16(1):66-71
references.pmid: 5764526
references.citation: Acta Anaesthesiol Scand Suppl. 1966;24:215-22
references.pmid: 6003600
references.citation: Br J Anaesth. 1972 Apr;44(4):386-90
references.pmid: 5032077
references.citation: Anesth Analg. 1970 May-Jun;49(3):345-50
references.pmid: 5534408
references.citation: J Dermatol Surg Oncol. 1984 Feb;10(2):85-6
references.pmid: 6693612
references.citation: BJU Int. 2012 Dec;110 Suppl 4:85-8
references.pmid: 23194132
references.citation: BMJ Support Palliat Care. 2014 Dec;4(4):342-8
references.pmid: 24644183
references.citation: Ann Emerg Med. 2001 Dec;38(6):633-8
references.pmid: 11719741
references.citation: Gastrointest Endosc. 2013 Dec;78(6):892-901
references.pmid: 23810328
references.citation: Acta Obstet Gynecol Scand. 1971;50(3):285-90
references.pmid: 4942713
references.citation: Anesth Analg. 1972 Mar-Apr;51(2):208-12
references.pmid: 4551090
references.citation: Br J Anaesth. 1969 Dec;41(12):1080-5
references.pmid: 4903969
references.citation: Aust Dent J. 2011 Sep;56(3):296-301
references.pmid: 21884146
references.citation: Emerg Med Australas. 2009 Feb;21(1):4-11
references.pmid: 19254307
references.citation: Acta Anaesthesiol Scand. 2008 Aug;52(7):920-5
references.pmid: 18702754