Inhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department

NCT03257319 | Completed Phase 3

• 1 other identifier: 2014/0009/HP
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 20

Brief Summary

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.

Conditions

Pain, Acute; Emergencies; Morphine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Evaluate antalgic efficacy criteria

  From the beginning of the titration until the end of the titration- assessed within one day

• Evaluate antalgic efficacy criteria

  From the beginning of the titration until the end of the titration- assessed up to one day

• Evaluate antalgic efficacy criteria

  From the beginning of the titration until the end of the titration- assessed up to one day

• Evaluate antalgic efficacy criteria

  From the beginning of the titration until the end of the titration- assessed up to one day

• Evaluate antalgic efficacy criteria

  30 minutes after the initiation of the titration

Study Arms (2)

inhaled morphine + IV placebo

EXPERIMENTAL

Arm A: inhaled titration of morphine chlorhydrate+ IV placebo

Drug: inhaled titration of morphine chlorhydrate; Drug: IV placebo

IV morphine +inhaled placebo

PLACEBO COMPARATOR

Arm B:IV titration of morphine chlorhydrate + inhaled placebo

Device: Inhaled placebo; Drug: IV titration of morphine chlorhydrate

Interventions

inhaled titration of morphine chlorhydrate DRUG

Patient in arm A will receive 1 to 3 titration

Also known as: IV placebo

inhaled morphine + IV placebo

IV placebo DRUG

Patient in arm A will receive 1 to 6 injection

Also known as: inhaled titration of morphine chlorhydrate

inhaled morphine + IV placebo

Inhaled placebo DEVICE

Patient in arm B will receive 1 to 3 titration

Also known as: IV titration of morphine chlorhydrate

IV morphine +inhaled placebo

IV titration of morphine chlorhydrate DRUG

Patient in arm BA will receive 1 to 6 injection

Also known as: Inhaled placebo

IV morphine +inhaled placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (20)

CH Agen-Nérac

Agen, France

Location

CHI Robert Ballanger

Aulnay-sous-Bois, France

Location

AP-HP

Bobigny, France

Location

CHU Hôpitaux BORDEAUX

Bordeaux, France

Location

CHU de Caen

Caen, France

Location

CHU Gabriel Montpied

Clermont-Ferrand, France

Location

CH Eure Seine Hôpital d'Evreux

Évreux, France

Location

CHU Grenoble

Grenoble, France

Location

GH Le Havre

Le Havre, France

Location

CH Le Mans

Le Mans, France

Location

CHRU de Lille

Lille, France

Location

Hospices civils de Lyon

Lyon, France

Location

CHU Nice

Nice, France

Location

Hopital COCHIN

Paris, France

Location

Hôpital Lariboisière

Paris, France

Location

La Pitié Salpétrière

Paris, France

Location

CHU-Hôpitaux de Rouen

Rouen, 76031, France

Location

Hôpital Bichat-Claude Bernard

Saint-Ouen, France

Location

Chu Strasbourg

Strasbourg, France

Location

chu de Toulouse

Toulouse, France

Location

Related Publications (1)

• 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.

  PMID: 30975187 DERIVED

MeSH Terms

Conditions

Acute Pain; Emergencies

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: August 22, 2017
• Study Start: September 19, 2017
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (20)