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

University Hospital, Rouen

Status and phase: Completed; Phase 3

Conditions: Morphine; Emergencies; Pain, Acute

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03257319

2014/0009/HP

Details and patient eligibility

About

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.

Enrollment: 226 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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226 participants in 2 patient groups, including a placebo group

inhaled morphine + IV placebo

Experimental group

Description:

Arm A: inhaled titration of morphine chlorhydrate+ IV placebo

Treatment:

Drug: IV placebo

Drug: inhaled titration of morphine chlorhydrate

IV morphine +inhaled placebo

Placebo Comparator group

Description:

Arm B:IV titration of morphine chlorhydrate + inhaled placebo

Treatment:

Device: Inhaled placebo

Drug: IV titration of morphine chlorhydrate