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

Phase 3

• Conditions: Pain, Acute; Emergencies; Morphine
• Interventions: Device: Inhaled placebo; Drug: inhaled titration of morphine chlorhydrate; Drug: IV placebo; Drug: IV titration of morphine chlorhydrate

• Registration Number: NCT03257319
• Lead Sponsor: University Hospital, Rouen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-20
• Study First Submitted QC: 2017-08-21
• Study First Posted: 2017-08-22
• Study Start: 2017-09-19
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-25
• Last Update Posted: 2018-05-30
• Primary Completion: 2019-09-19
• Study Completion: 2019-09-19

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 850

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
inhaled morphine + IV placebo	IV placebo	Arm A: inhaled titration of morphine chlorhydrate+ IV placebo
IV morphine +inhaled placebo	Inhaled placebo	Arm B:IV titration of morphine chlorhydrate + inhaled placebo
inhaled morphine + IV placebo	inhaled titration of morphine chlorhydrate	Arm A: inhaled titration of morphine chlorhydrate+ IV placebo
IV morphine +inhaled placebo	IV titration of morphine chlorhydrate	Arm B:IV titration of morphine chlorhydrate + inhaled placebo

Primary Outcome Measures

Name	Time	Method
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	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).

Secondary Outcome Measures

Name	Time	Method
Evaluate antalgic efficacy criteria	2hours after the initiation of the titration	Number of patients with EVA ≤ 30 or EN ≤ 3 after 120 minutes
Assess the feasibility of an aerosol titration (compliance to the protocol)	From the beginning of the titration until the end of the aerosol titration- within one hour after the start of the titration	Number of deviations from protocol
Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events)	Until 3hours after the end of the titration	Proportion of Sleepy patients (Ramsay score = 3)
Safety- Proportion of serious adverse events in each arm	Until 3hours after the end of the titration	Proportion of serious adverse events in each arm
Safety- 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	incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention,; ...)

Trial Locations

Locations (19)

CH Le Mans; 🇫🇷 Le Mans, France

CHI Robert Ballanger; 🇫🇷 Aulnay-sous-Bois, France

CH Agen-Nérac; 🇫🇷 Agen, France

CHU de Caen; 🇫🇷 Caen, France

CHRU de Lille; 🇫🇷 Lille, France

CHU Hôpitaux BORDEAUX; 🇫🇷 Bordeaux, France

CHU Grenoble; 🇫🇷 Grenoble, France

Hospices civils de Lyon; 🇫🇷 Lyon, France

CHU Gabriel Montpied; 🇫🇷 Clermont-Ferrand, France

GH Le Havre; 🇫🇷 Le Havre, France

Hopital COCHIN; 🇫🇷 Paris, France

Hôpital Lariboisière; 🇫🇷 Paris, France

CHU-Hôpitaux de Rouen; 🇫🇷 Rouen, France

chu de Toulouse; 🇫🇷 Toulouse, France

La Pitié Salpétrière; 🇫🇷 Paris, France

Hôpital Bichat-Claude Bernard; 🇫🇷 Saint-Ouen, France

CHU Nice; 🇫🇷 Nice, France

Chu Strasbourg; 🇫🇷 Strasbourg, France

CH Eure Seine Hôpital d'Evreux; 🇫🇷 Évreux, France