Comparison of MEOPA + Paracetamol Versus Morphine Treatment in Acute Coronary Syndrome Analgesia. (SCADOLII)

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.

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Morphine; Drug: MEOPA and paracetamol

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.

• Study Type: Interventional
• Enrollment (Actual): 680
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Agen, France
    • Centre Hospitalier d'Agen
  • Besançon, France
    • Centre Hospitalier Jean Minjoz
  • Bobigny, France
    • CHU Avicenne
  • Bordeaux, France
    • Hopital Pellegrin
  • Bourg-en-Bresse, France
    • Centre Hospitalier Bourg-en-Bresse
  • Chambéry, France
    • Centre Hospitalier de Chambery
  • Chartres, France
    • Centre Hospitalier Louis Pasteur
  • Chateauroux, France
    • Centre Hospitalier Chateauroux
  • Clermont-Ferrand, France
    • CHU d'Estaing
  • Clichy, France
    • Centre Hospitalier Beaujon
  • Contamine sur Arve, France
    • Centre hospitalier Alpes Léman
  • Corbeil-Essonnes, France
    • Centre Hospitalier Sud Francilien
  • Dijon, France
    • Centre Hospitalier Dijon
  • Foix, France
    • Centre Hospitalier du val d'Ariège
  • Garches, France
    • Centre Hospitalier Raymond Poincaré
  • Grenoble, France
    • Centre Hospitalier de Grenoble
  • La Roche-sur-Yon, France
    • Centre Hospitalier Départemental La Roche/Yon
  • Lille, France
    • CHRU Lille
  • Limoges, France
    • CHU Dupuytren
  • Lyon, France
    • Centre Hospitalier Edouard Herriot
  • Marseille, France
    • Centre Hospitalier de la Timone
  • Melun, France
    • Centre Hospitalier Marc Jacquet
  • Metz, France
    • CHR Bon Secours
  • Montpellier, France
    • CHRU Montpellier
  • Nancy, France
    • CHU Nancy
  • Nantes, France
    • Chu Nantes
  • Nice, France
    • Centre Hospitalier de Nice
  • Paris, France
    • Centre Hospitalier Necker
  • Paris, France
    • Centre Hospitalier Pitié-Salpétrière
  • Paris, France
    • Groupe hospitamier Lariboisière-Fernand Widal-St-Louis
  • Poitiers, France
    • CHU Poitiers
  • Pontoise, France
    • Centre Hospitalier René Dubos
  • Pringy, France
    • Centre Hospitalier Annecy-Gennevois
  • Saint-Gaudens, France
    • Centre Hospitalier COMMINGES PYRENEES
  • Toulon, France
    • Centre Hospitalier Poulon la Seyne-sur-mer
  • Toulouse, France
    • Chu Toulouse
  • Tours, France
    • CHRU Tours
  • Valence, France
    • Centre Hospitalier de Valence
  • Vienne, France
    • Centre Hospitalier Lucien Hussel
• Réunion
  • Saint-Denis, Réunion
    • CHU Felix Guyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine; Morphine group: administration of morphine will start with a 0.05 mg/kg bolus followed by reinjection of 2 mg every 5 minutes until effective analgesia is obtained, defined as NRS ≤ 3.	Drug: Morphine; Bolus of 2 mg intravenously if EN = 4 or 5 and 3 mg bolus if EN> 6 followed by reinjection of 2mg every 5 minutes until effective analgesia.; Other Names: Morphine Renaudin 1mg/ml
Experimental: MEOPA and paracetamol; The patient will be equipped with a facemask delivering MEOPA.The gas flow received by the patient is adapted to his/her ventilation. During the same time, an intravenous injection of 1 g paracetamol will be administered.	Drug: MEOPA and paracetamol; The patient will be equipped with a facemask after he/she has been informed. The facemask is adapted to the patient. The patient breathes normally in the mask which is held in place by a member of the SMUR team who has received previous training in use of MEOPA. The gas flow received by the patient is adapted to his/her ventilation.; Other Names: Entonox 170 bar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective analgesia (NRS score≤ 3) at 30 minutes after the start of analgesia	The primary outcome measure is effective analgesia, defined by the consensus conference as an NRS score ≤ 3 at 30 minutes after the start of analgesia.	30 minutes after randomisation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event	Occurrence of an adverse effect, in particular, respiratory depression (RR, respiratory rate < 10 cycles par minute or respiratory score ≥ R1), nausea, vomiting, sedation (sedation scale (EDS) score ≥2), dizziness, pruritus.	all 5 minutes during 30 minutes
NRS distribution	Distribution of the NRS at 30 minutes and on arrival at the cardiology unit	30 minutes after randomization
Effective analgesia	The time of effective analgesia will be defined for each subject	all 5 minutes during 30 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Sandrine Charpentier, PH,MD, Chu Toulouse

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: J Am Coll Cardiol. 2008 Mar 4;51(9):977.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 22, 2014
• First Posted (Estimate): July 23, 2014

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: February 2, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: pain; acute coronary syndrome; prehospital setting; premixed nitrous oxide and oxygen
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Anesthetics, Combined; Acetaminophen; Morphine; Entonox
• Other Study ID Numbers: RC31/13/7050; 13705001 (Other Grant/Funding Number: French Ministry of Health, PHRC 2013)