Inhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department (CLIN-AEROMORPH)

Inhaled Versus Intravenous Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department

Prospective single-blind, multicenter, national, randomized, controlled trial in 15 Emergency Department to compare two ways of morphine titration. The eligible patient is included immediately after his arrival in the Emergency Department, after being questioned by the triage nurse about the presence and the intensity of pain, when the VAS is greater than 70 (or EN>7) and after written consent.

After installation into the examination room, patient is randomized in one of two parallel groups (stratified by sex and center using software) and receives one of the two treatments, either inhaled morphine + IV placebo or IV morphine+ inhaled placebo (control group).

In both groups, titration is defined by a dose of repeated boluses as long as the relief is not achieved (VAS> 30 or EN >3) and the criteria to stop titration are not met.

A 5 minutes time interval between the boluses is chosen. Each aerosol takes 5 minutes at a constant air flow, aerosol mask, plastic tubing and PVC transparent tank are used.

Thus patient receives a maximum of 3 aerosol (one aerosol every 10 minutes) and a maximum of 6 IV injections (one injection every 5 minutes) The stopping criteria, except pain relief, are linked to the occurrence of side effects and specific cares are described into the protocol (in case of severe ventilatory depression naloxone titration is provided). Exit criteria from the emergency room and from the hospital are defined. An information sheet is delivered.

Study Overview

• Status: Completed
• Conditions: Emergencies; Pain, Acute; Morphine
• Intervention / Treatment: Drug: inhaled titration of morphine chlorhydrate; Drug: IV placebo; Device: Inhaled placebo; Drug: IV titration of morphine chlorhydrate

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Agen, France
    • CH Agen-Nérac
  • Aulnay-sous-Bois, France
    • CHI Robert Ballanger
  • Bobigny, France
    • AP-HP
  • Bordeaux, France
    • CHU Hôpitaux BORDEAUX
  • Caen, France
    • CHU de Caen
  • Clermont-Ferrand, France
    • CHU Gabriel Montpied
  • Grenoble, France
    • CHU Grenoble
  • Le Havre, France
    • Gh Le Havre
  • Le Mans, France
    • CH Le mans
  • Lille, France
    • CHRU de Lille
  • Lyon, France
    • Hospices Civils de Lyon
  • Nice, France
    • CHU Nice
  • Paris, France
    • Hopital Lariboisiere
  • Paris, France
    • Hopital Cochin
  • Paris, France
    • La Pitié Salpêtrière
  • Rouen, France, 76031
    • CHU-Hôpitaux de Rouen
  • Saint-Ouen, France
    • Hopital Bichat-Claude Bernard
  • Strasbourg, France
    • CHU Strasbourg
  • Toulouse, France
    • CHU de Toulouse
  • Évreux, France
    • CH Eure Seine Hôpital d'Evreux

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 and <75 years old;
• EVA ≥ 70/100 or EN ≥ 7/10;
• Patient who received clear information from the investigator and read and signed the consent form;
• Patient affiliated with, or beneficiary of a social security category;
• For women:

O of childbearing age: effective contraception (oral contraception, intrauterine device or use of condoms) O menopausal status (amenorrhoea less than 12 months before the inclusion visit) O objectivized sterility (diagnosis or surgically)

Exclusion Criteria:

• Chronic pain (> 3 months)
• Taking opioids longer than 10 days (including "weak" opioids tramadol and / or codeine);
• Taking Rifampicin;
• Impaired ability to discern, cognitive impairment;
• Morphine-related contraindications:

O Obstructive chronic obstructive or restrictive respiratory failure known or suspected compensated or not, O Hypersensitivity to the active substance or to any of the excipients, O Severe hepatocellular insufficiency (known or suspected), O Chronic renal failure known or suspected, O Uncontrolled epilepsy, O Cranial trauma (intracranial hypertension), O Associations with buprenorphine, nalbuphine, pentazocine and naltrexone

• Active drug history or practice (s);
• Evidence of reduced fracture or dislocation in emergency rooms;
• Suspected occlusive syndrome
• SaO2 <95%;
• FR <12 / min;
• Glasgow <15 or other alertness disorders;
• HR heart rate <50 bpm and / or Auriculo-Ventricular block (PR XML File Identifier: zR6XOYKSEQ9GjQHghP8c465EwF0= Page 15/30 interval> 200 ms);
• Arterial hypotension with systolic blood pressure TA syst <100 mm Hg;
• Pregnant or nursing
• Persons deprived of their liberty by an administrative or judicial decision, a person placed under the safeguard of justice, guardianship;
• Patients with poor comprehension of spoken or written French;
• Patients participating in another interventional clinical study;
• Contra-indication related to the use of saline solution
• Contra-indications related to the use of aerosol:

O Necessity to access the face O Allergy known to plastic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: inhaled morphine + IV placebo; Arm A: inhaled titration of morphine chlorhydrate+ IV placebo	Drug: inhaled titration of morphine chlorhydrate; Patient in arm A will receive 1 to 3 titration; Other Names: IV placebo; Drug: IV placebo; Patient in arm A will receive 1 to 6 injection; Other Names: inhaled titration of morphine chlorhydrate
Placebo Comparator: IV morphine +inhaled placebo; Arm B:IV titration of morphine chlorhydrate + inhaled placebo	Device: Inhaled placebo; Patient in arm B will receive 1 to 3 titration; Other Names: IV titration of morphine chlorhydrate; Drug: IV titration of morphine chlorhydrate; Patient in arm BA will receive 1 to 6 injection; Other Names: Inhaled placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of relief obtained or "success rate" at 1 hour from the start of drug administration, and not at the end of titration, such as EVA1 ≤ 30/100 (or EN1 ≤ 3/10).	Rate of relief obtained or "success rate" at 1 hour from the start of drug administration, and not at the end of titration, such as EVA1 ≤ 30/100 (or EN1 ≤ 3/10).	1 hour after the initiation of the titration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate antalgic efficacy criteria	Quantity of morphine administered from the beginning of the titration until the end of the titration	From the beginning of the titration until the end of the titration- assessed within one day
Evaluate antalgic efficacy criteria	Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained	From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria	Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained for patient treated only with morphine IV	From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria	Number of patients with EVA ≤ 30 or EN ≤ 3 at the end of titration	From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria	Number of patients with EVA ≤ 30 or EN ≤ 3 at 30 minutes	30 minutes after the initiation of the titration
Evaluate antalgic efficacy criteria	Number of patients treated only by exclusive inhalation titration with EVA ≤ 30 or EN ≤ 3	From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria	Quantity of of co-analgesia administered from the beginning of the titration	From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria	Number of patients with EVA ≤ 30 or EN ≤ 3 after 60 minutes	1hour after the initiation of the titration
Evaluate antalgic efficacy criteria	Number of patients with EVA ≤ 30 or EN ≤ 3 after 120 minutes	2hours after the initiation of the titration
Assess the feasibility of an aerosol titration (compliance to the protocol)	Number of deviations from protocol	From the beginning of the titration until the end of the aerosol titration- within one hour after the start of the titration
Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events)	Proportion of Sleepy patients (Ramsay score = 3)	Until 3hours after the end of the titration
Safety- incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention, ...)	incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention, ...)	Until 3hours after the end of the titration
Safety- Proportion of serious adverse events in each arm	Proportion of serious adverse events in each arm	Until 3hours after the end of the titration

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Publications and helpful links

General Publications

• Lvovschi VE, Joly J, Lemaire N, Maignan M, Canavaggio P, Leroi AM, Tavolacci MP, Joly LM. Nebulized versus intravenous morphine titration for the initial treatment of severe acute pain in the emergency department: study protocol for a multicenter, prospective randomized and controlled trial, CLIN-AEROMORPH. Trials. 2019 Apr 11;20(1):209. doi: 10.1186/s13063-019-3326-3.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2017
• Primary Completion (Actual): July 29, 2022
• Study Completion (Actual): July 29, 2022

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergencies; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 2014/0009/HP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No