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

Pain, Acute Clinical Trial

— CLIN-AEROMORPH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03257319
• Other study ID #: 2014/009/HP
• Status: Recruiting
• Phase: Phase 3
• Start date: September 19, 2017
• Est. completion date: September 19, 2019

Study information

• Verified date: May 2018
• Source: University Hospital, Rouen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 850
• Est. completion date: September 19, 2019
• Est. primary completion date: September 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Pain
• Emergencies
• Morphine
• Pain, Acute

Intervention

Drug:
• inhaled titration of morphine chlorhydrate
Patient in arm A will receive 1 to 3 titration
• IV placebo
Patient in arm A will receive 1 to 6 injection

Device:
• Inhaled placebo
Patient in arm B will receive 1 to 3 titration

Drug:
• IV titration of morphine chlorhydrate
Patient in arm BA will receive 1 to 6 injection

Locations

Country	Name	City	State
France	CH Agen-Nérac	Agen
France	CHI Robert Ballanger	Aulnay-sous-Bois
France	CHU Hôpitaux BORDEAUX	Bordeaux
France	CHU de Caen	Caen
France	CHU Gabriel Montpied	Clermont-Ferrand
France	CH Eure Seine Hôpital d'Evreux	Évreux
France	CHU Grenoble	Grenoble
France	GH Le Havre	Le Havre
France	CH Le Mans	Le Mans
France	CHRU de Lille	Lille
France	Hospices civils de Lyon	Lyon
France	CHU Nice	Nice
France	Hopital COCHIN	Paris
France	Hôpital Lariboisière	Paris
France	La Pitié Salpétrière	Paris
France	CHU-Hôpitaux de Rouen	Rouen
France	Hôpital Bichat-Claude Bernard	Saint-Ouen
France	Chu Strasbourg	Strasbourg
France	chu de Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Evaluate antalgic efficacy criteria	Number of patients with EVA = 30 or EN = 3 at 30 minutes	30 minutes after the initiation of the titration
Secondary	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
Secondary	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
Secondary	Evaluate antalgic efficacy criteria	Number of patients with EVA = 30 or EN = 3 after 60 minutes	1hour after the initiation of the titration
Secondary	Evaluate antalgic efficacy criteria	Number of patients with EVA = 30 or EN = 3 after 120 minutes	2hours after the initiation of the titration
Secondary	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
Secondary	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
Secondary	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
Secondary	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