Back to resultsInhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department (CLIN-AEROMORPH)
Primary Purpose
Pain, Acute, Emergencies, Morphine
Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
inhaled titration of morphine chlorhydrate
IV placebo
Inhaled placebo
IV titration of morphine chlorhydrate
Sponsored by
About this trial
This is an interventional treatment trial for Pain, Acute
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
Sites / Locations
- CH Agen-NéracRecruiting
- CHI Robert BallangerRecruiting
- CHU Hôpitaux BORDEAUXRecruiting
- CHU de CaenRecruiting
- CHU Gabriel MontpiedRecruiting
- CHU GrenobleRecruiting
- GH Le HavreRecruiting
- CH Le MansRecruiting
- CHRU de LilleRecruiting
- Hospices civils de LyonRecruiting
- CHU NiceRecruiting
- Hopital COCHINRecruiting
- Hôpital LariboisièreRecruiting
- La Pitié SalpétrièreRecruiting
- CHU-Hôpitaux de RouenRecruiting
- Hôpital Bichat-Claude BernardRecruiting
- Chu StrasbourgRecruiting
- chu de ToulouseRecruiting
- CH Eure Seine Hôpital d'EvreuxRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
inhaled morphine + IV placebo
IV morphine +inhaled placebo
Arm Description
Arm A: inhaled titration of morphine chlorhydrate+ IV placebo
Arm B:IV titration of morphine chlorhydrate + inhaled placebo
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Evaluate antalgic efficacy criteria
Quantity of morphine administered from the beginning of the titration until the end of the titration
Evaluate antalgic efficacy criteria
Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained
Evaluate antalgic efficacy criteria
Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained for patient treated only with morphine IV
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 at the end of titration
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 at 30 minutes
Evaluate antalgic efficacy criteria
Number of patients treated only by exclusive inhalation titration with EVA ≤ 30 or EN ≤ 3
Evaluate antalgic efficacy criteria
Quantity of of co-analgesia administered from the beginning of the titration
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 after 60 minutes
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 after 120 minutes
Assess the feasibility of an aerosol titration (compliance to the protocol)
Number of deviations from protocol
Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events)
Proportion of Sleepy patients (Ramsay score = 3)
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,
...)
Safety- Proportion of serious adverse events in each arm
Proportion of serious adverse events in each arm
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03257319
Brief Title
Inhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
Acronym
CLIN-AEROMORPH
Official Title
Inhaled Versus Intravenous Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 19, 2017 (Actual)
Primary Completion Date
September 19, 2019 (Anticipated)
Study Completion Date
September 19, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Rouen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Acute, Emergencies, Morphine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
850 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
inhaled morphine + IV placebo
Arm Type
Experimental
Arm Description
Arm A: inhaled titration of morphine chlorhydrate+ IV placebo
Arm Title
IV morphine +inhaled placebo
Arm Type
Placebo Comparator
Arm Description
Arm B:IV titration of morphine chlorhydrate + inhaled placebo
Intervention Type
Drug
Intervention Name(s)
inhaled titration of morphine chlorhydrate
Other Intervention Name(s)
IV placebo
Intervention Description
Patient in arm A will receive 1 to 3 titration
Intervention Type
Drug
Intervention Name(s)
IV placebo
Other Intervention Name(s)
inhaled titration of morphine chlorhydrate
Intervention Description
Patient in arm A will receive 1 to 6 injection
Intervention Type
Device
Intervention Name(s)
Inhaled placebo
Other Intervention Name(s)
IV titration of morphine chlorhydrate
Intervention Description
Patient in arm B will receive 1 to 3 titration
Intervention Type
Drug
Intervention Name(s)
IV titration of morphine chlorhydrate
Other Intervention Name(s)
Inhaled placebo
Intervention Description
Patient in arm BA will receive 1 to 6 injection
Primary Outcome Measure Information:
Title
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).
Description
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).
Time Frame
1 hour after the initiation of the titration
Secondary Outcome Measure Information:
Title
Evaluate antalgic efficacy criteria
Description
Quantity of morphine administered from the beginning of the titration until the end of the titration
Time Frame
From the beginning of the titration until the end of the titration- assessed within one day
Title
Evaluate antalgic efficacy criteria
Description
Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained
Time Frame
From the beginning of the titration until the end of the titration- assessed up to one day
Title
Evaluate antalgic efficacy criteria
Description
Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained for patient treated only with morphine IV
Time Frame
From the beginning of the titration until the end of the titration- assessed up to one day
Title
Evaluate antalgic efficacy criteria
Description
Number of patients with EVA ≤ 30 or EN ≤ 3 at the end of titration
Time Frame
From the beginning of the titration until the end of the titration- assessed up to one day
Title
Evaluate antalgic efficacy criteria
Description
Number of patients with EVA ≤ 30 or EN ≤ 3 at 30 minutes
Time Frame
30 minutes after the initiation of the titration
Title
Evaluate antalgic efficacy criteria
Description
Number of patients treated only by exclusive inhalation titration with EVA ≤ 30 or EN ≤ 3
Time Frame
From the beginning of the titration until the end of the titration- assessed up to one day
Title
Evaluate antalgic efficacy criteria
Description
Quantity of of co-analgesia administered from the beginning of the titration
Time Frame
From the beginning of the titration until the end of the titration- assessed up to one day
Title
Evaluate antalgic efficacy criteria
Description
Number of patients with EVA ≤ 30 or EN ≤ 3 after 60 minutes
Time Frame
1hour after the initiation of the titration
Title
Evaluate antalgic efficacy criteria
Description
Number of patients with EVA ≤ 30 or EN ≤ 3 after 120 minutes
Time Frame
2hours after the initiation of the titration
Title
Assess the feasibility of an aerosol titration (compliance to the protocol)
Description
Number of deviations from protocol
Time Frame
From the beginning of the titration until the end of the aerosol titration- within one hour after the start of the titration
Title
Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events)
Description
Proportion of Sleepy patients (Ramsay score = 3)
Time Frame
Until 3hours after the end of the titration
Title
Safety- incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention, ...)
Description
incidence of minor side effects in each arm of which neurovegetative usually known and related to opiates (nausea, vomiting, urine retention,
...)
Time Frame
Until 3hours after the end of the titration
Title
Safety- Proportion of serious adverse events in each arm
Description
Proportion of serious adverse events in each arm
Time Frame
Until 3hours after the end of the titration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
CH Agen-Nérac
City
Agen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
P-A FORT
Phone
05 53 69 70 93
Email
pierrearnaudf@yahoo.fr
Facility Name
CHI Robert Ballanger
City
Aulnay-sous-Bois
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna BOUCHARA
Phone
01 49 36 72 12
Ext
+33
Email
anna.bouchara@ch-aulnay.fr
Facility Name
CHU Hôpitaux BORDEAUX
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M GALINSKI
Phone
05 56 79 48 26
Email
michel.galinski@chu-bordeaux.fr
Facility Name
CHU de Caen
City
Caen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C LE ROUX
Phone
02 31 06 52 40
Email
leroux-c@chu-caen.fr
Facility Name
CHU Gabriel Montpied
City
Clermont-Ferrand
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J. RACONNAT
Phone
04 73 75 07 50
Email
jraconnat@chu-clermontferrand.fr
Facility Name
CHU Grenoble
City
Grenoble
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M MAIGNAN
Phone
04 76 76 59 31
Email
mmaignan@chu-grenoble.fr
Facility Name
GH Le Havre
City
Le Havre
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
XAVIER BENET
Phone
02 32 73 32 32
Email
xav.benet@gmail.com
Facility Name
CH Le Mans
City
Le Mans
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
O MOULIN
Phone
02 43 43 43 43
Email
omoulin@ch-lemans.fr
Facility Name
CHRU de Lille
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
eric wiel
Phone
03 20 44 59 62
Email
eric.wiel@chru-lille.fr
Facility Name
Hospices civils de Lyon
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
karim tazarourte
Phone
04 72 11 00 31
Email
karim.tazarourte@chu-lyon.fr
Facility Name
CHU Nice
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J LEVRAUT
Phone
04 92 03 77 77
Email
levraut.j@chu-nice.fr
Facility Name
Hopital COCHIN
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
F LECOMTE
Phone
04 58 41 41 41
Email
francois.lecomte@aphp.fr
Facility Name
Hôpital Lariboisière
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
N Ouled-Jaballah
Phone
01 49 95 63 91
Email
nora.ouled@aphp.fr
Facility Name
La Pitié Salpétrière
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
pierre Hausfater
Phone
01 42 17 72 40
Email
pierre.hausfater@psl.aphp.fr
Facility Name
CHU-Hôpitaux de Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lionel DA CRUZ
Phone
0232888265
Ext
+33
Email
secretariat.drc@chu-rouen.fr
First Name & Middle Initial & Last Name & Degree
Cécile POURCHER
Phone
0232888265
Ext
+33
Email
secretariat.drc@chu-rouen.fr
First Name & Middle Initial & Last Name & Degree
Virginie-Eve LVOVSCHI
Facility Name
Hôpital Bichat-Claude Bernard
City
Saint-Ouen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A-E CASALINO
Phone
1 40 25 77 60
Ext
+33
Email
enrique.casalino@bch.aphp.fr
Facility Name
Chu Strasbourg
City
Strasbourg
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S kepka
Phone
03 69 55 13 35
Email
sabrinakepka@yahoo.fr
Facility Name
chu de Toulouse
City
Toulouse
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S charpentier
Phone
0561323354
Email
charpentier.s@chu-toulouse.fr
Facility Name
CH Eure Seine Hôpital d'Evreux
City
Évreux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arnaud Depil-duva
Phone
02 32 33 85 10
Email
arnaud.depil-duval@ch-eureseine.fr
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30975187
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.
Results Reference
derived
Learn more about this trial
Inhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
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