Clinical trial NCT02198378: Comparison of MEOPA + Paracetamol Versus Morphine Treatment in Acute Coronary Syndrome Analgesia.
Official title: Analgesia of Acute Coronary Syndromes With ST-segment Elevation in a Pre-hospital Setting. Randomized Non-inferiority Trial of the Association MEOPA + Paracetamol Versus Morphine.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: premixed nitrous oxide and oxygen
pain
prehospital setting
acute coronary syndrome
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2014-07-23
Enrollment: 680
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In the management of acute coronary syndromes with ST-segment elevation (STEMI), early analgesia reduces the effects of hyperadrenalism which increases the size of myocardial infarction. In order to reduce pain intensity, the recommendations advocate emergency use of morphine. In STEMI patients, other analgesic treatments could provide analgesia that is at least as effective as morphine. The equimolar oxygen/nitrous oxide mixture (MEOPA) is widely used in emergency medicine and has minor secondary effects that are very rapidly reversible when inhalation is discontinued. Used in association with paracetamol, it could be an at least equally effective alternative to the use of morphine.

Detailed description: The investigators wish to compare the use of morphine according to current recommendations with the use of MEOPA associated with intravenous paracetamol in the management of patients with STEMI. The investigators hypothesize that the association of MEOPA and paracetamol, which is easy to use in a pre-hospital setting, will give patients pain relief as effectively as morphine.

This alternative treatment would avoid the use of morphine, whose potentially damaging consequences on myocardial function have been suggested by experimental studies and by an observational study. The physician of the mobile emergency team (SMUR) verifies the inclusion and non- inclusion criteria for the study. The patient must present STEMI defined in accordance with the recommendations and chest pain of intensity ≥ 4 on the NRS. The specific treatment for STEMI will be given before inclusion in the study, with the exception of analgesic treatment. In particular, inclusion in the study must not delay the initiation of strategies of recanalization and reperfusion.

The SMUR physician in charge of the patient will administer the treatment defined by randomization.

After 30 minutes, the patient will be managed in accordance with the recommendations and will be hospitalized, generally in a cardiology intensive care unit. At one month, the clinical research technician will record the patient's vital status and collect the patient's hospital records.

Eligibility criteria: Inclusion Criteria:

* Patient with STEMI \< 12 h treated before hospital admission and pain ≥ 4 on the numerical rating scale.

Exclusion Criteria:

* Acute severe hemodynamic, respiratory or neurological failure
* Heart failure: Killip class III and IV
* Known allergy to morphine or nitrous oxide
* Patient who has already received morphine or MEOPA before the arrival of the hospital team during the 4 hours preceding the pre-hospital intervention
* Contraindications to nitrous oxide
* Patient unable to assess pain intensity on the numerical rating scale
* Patient under legal guardianship
* Pregnancy
* Patient transported by air ambulance

Primary outcomes:
measure: Effective analgesia (NRS score≤ 3) at 30 minutes after the start of analgesia
timeFrame: 30 minutes after randomisation.
Secondary outcomes:
measure: Adverse event
timeFrame: all 5 minutes during 30 minutes
measure: NRS distribution
timeFrame: 30 minutes after randomization
measure: Effective analgesia
timeFrame: all 5 minutes during 30 minutes
Other outcomes:
Locations:
city: Agen
country: France
facility: Centre Hospitalier d'Agen
city: Besançon
country: France
facility: Centre Hospitalier Jean Minjoz
city: Bobigny
country: France
facility: CHU Avicenne
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Bourg-en-Bresse
country: France
facility: Centre Hospitalier Bourg-en-Bresse
city: Chambéry
country: France
facility: Centre Hospitalier de Chambéry
city: Chartres
country: France
facility: Centre Hospitalier Louis Pasteur
city: Chateauroux
country: France
facility: Centre Hospitalier Chateauroux
city: Clermont-Ferrand
country: France
facility: CHU d'Estaing
city: Clichy
country: France
facility: Centre Hospitalier Beaujon
city: Contamine sur Arve
country: France
facility: Centre Hospitalier Alpes Léman
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud Francilien
city: Dijon
country: France
facility: Centre Hospitalier Dijon
city: Foix
country: France
facility: Centre Hospitalier du Val d'Ariège
city: Garches
country: France
facility: Centre Hospitalier Raymond Poincaré
city: Grenoble
country: France
facility: Centre Hospitalier de Grenoble
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental La Roche/Yon
city: Lille
country: France
facility: CHRU Lille
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Centre Hospitalier Edouard Herriot
city: Marseille
country: France
facility: Centre Hospitalier de la Timone
city: Melun
country: France
facility: Centre Hospitalier Marc Jacquet
city: Metz
country: France
facility: CHR Bon Secours
city: Montpellier
country: France
facility: CHRU Montpellier
city: Nancy
country: France
facility: CHU Nancy
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: Centre Hospitalier de Nice
city: Paris
country: France
facility: Centre Hospitalier Necker
city: Paris
country: France
facility: Centre Hospitalier Pitié-Salpétrière
city: Paris
country: France
facility: Groupe hospitamier Lariboisière-Fernand Widal-St-Louis
city: Poitiers
country: France
facility: CHU Poitiers
city: Pontoise
country: France
facility: Centre Hospitalier René Dubos
city: Pringy
country: France
facility: Centre Hospitalier Annecy-Gennevois
city: Saint-Gaudens
country: France
facility: Centre Hospitalier Comminges Pyrénées
city: Toulon
country: France
facility: Centre Hospitalier Poulon la Seyne-sur-mer
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: CHRU Tours
city: Valence
country: France
facility: Centre Hospitalier de Valence
city: Vienne
country: France
facility: Centre Hospitalier Lucien Hussel
city: Saint-Denis
country: Réunion
facility: CHU Félix Guyon
Study officials:
affiliation: CHU Toulouse
name: Sandrine Charpentier, PH,MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Danchin N, Puymirat E, Aissaoui N, Adavane S, Durand E. [Epidemiology of acute coronary syndromes in France and in Europe]. Ann Cardiol Angeiol (Paris). 2010 Dec;59 Suppl 2:S37-41. doi: 10.1016/S0003-3928(10)70008-1. French.
citation: Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J. 2000 Sep;21(18):1502-13. doi: 10.1053/euhj.2000.2305.
citation: Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology; Bassand JP, Hamm CW, Ardissino D, Boersma E, Budaj A, Fernandez-Aviles F, Fox KA, Hasdai D, Ohman EM, Wallentin L, Wijns W. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007 Jul;28(13):1598-660. doi: 10.1093/eurheartj/ehm161. Epub 2007 Jun 14. No abstract available.
citation: Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M; ESC Committee for Practice Guidelines (CPG). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008 Dec;29(23):2909-45. doi: 10.1093/eurheartj/ehn416. Epub 2008 Nov 12. No abstract available.
citation: Canadian Cardiovascular Society; American Academy of Family Physicians; American College of Cardiology; American Heart Association; Antman EM, Hand M, Armstrong PW, Bates ER, Green LA, Halasyamani LK, Hochman JS, Krumholz HM, Lamas GA, Mullany CJ, Pearle DL, Sloan MA, Smith SC Jr, Anbe DT, Kushner FG, Ornato JP, Pearle DL, Sloan MA, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B, Tarkington LG, Yancy CW. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008 Jan 15;51(2):210-47. doi: 10.1016/j.jacc.2007.10.001. No abstract available.
citation: Charpentier S, Galinski M, Bounes V, Ricard-Hibon A, El-Khoury C, Elbaz M, Ageron FX, Manzo-Silberman S, Soulat L, Lapostolle F, Gerard A, Bregeaud D, Bongard V, Bonnefoy-Cudraz E; SCADOL II investigators. Nitrous oxide/oxygen plus acetaminophen versus morphine in ST elevation myocardial infarction: open-label, cluster-randomized, non-inferiority study. Scand J Trauma Resusc Emerg Med. 2020 May 12;28(1):36. doi: 10.1186/s13049-020-00731-y.