Clinical trial NCT03257319: Inhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
Official title: Inhaled Versus Intravenous Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pain, Acute
Emergencies
Morphine
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
First posted: 2017-08-22
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: 1 hour after the initiation of the titration
Secondary outcomes:
measure: Evaluate antalgic efficacy criteria
timeFrame: From the beginning of the titration until the end of the titration- assessed within one day
measure: Evaluate antalgic efficacy criteria
timeFrame: From the beginning of the titration until the end of the titration- assessed up to one day
measure: Evaluate antalgic efficacy criteria
timeFrame: From the beginning of the titration until the end of the titration- assessed up to one day
measure: Evaluate antalgic efficacy criteria
timeFrame: From the beginning of the titration until the end of the titration- assessed up to one day
measure: Evaluate antalgic efficacy criteria
timeFrame: 30 minutes after the initiation of the titration
measure: Evaluate antalgic efficacy criteria
timeFrame: From the beginning of the titration until the end of the titration- assessed up to one day
measure: Evaluate antalgic efficacy criteria
timeFrame: From the beginning of the titration until the end of the titration- assessed up to one day
measure: Evaluate antalgic efficacy criteria
timeFrame: 1hour after the initiation of the titration
measure: Evaluate antalgic efficacy criteria
timeFrame: 2hours after the initiation of the titration
measure: Assess the feasibility of an aerosol titration (compliance to the protocol)
timeFrame: From the beginning of the titration until the end of the aerosol titration- within one hour after the start of the titration
measure: Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events)
timeFrame: Until 3hours after the end of the titration
measure: Safety- incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention, ...)
timeFrame: Until 3hours after the end of the titration
measure: Safety- Proportion of serious adverse events in each arm
timeFrame: Until 3hours after the end of the titration
Other outcomes:
Locations:
city: Agen
country: France
facility: CH Agen-Nérac
city: Aulnay-sous-Bois
country: France
facility: CHI Robert Ballanger
city: Bordeaux
country: France
facility: CHU Hôpitaux BORDEAUX
city: Caen
country: France
facility: CHU de Caen
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied
city: Grenoble
country: France
facility: CHU Grenoble
city: Le Havre
country: France
facility: GH Le Havre
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Hospices civils de Lyon
city: Nice
country: France
facility: CHU Nice
city: Paris
country: France
facility: Hopital COCHIN
city: Paris
country: France
facility: Hôpital Lariboisière
city: Paris
country: France
facility: La Pitié Salpétrière
city: Rouen
country: France
facility: CHU-Hôpitaux de Rouen
city: Saint-Ouen
country: France
facility: Hôpital Bichat-Claude Bernard
city: Strasbourg
country: France
facility: Chu Strasbourg
city: Toulouse
country: France
facility: chu de Toulouse
city: Évreux
country: France
facility: CH Eure Seine Hôpital d'Evreux
Study officials:
References:
citation: 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.