Pain, AcutePhase 3CLIN-AEROMORPHNCT03257319
Inhaled vs IV Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
A Phase 3 study testing inhaled titration of morphine chlorhydrate and IV titration of morphine chlorhydrate in people with Pain, Acute and Emergencies, run by University Hospital, Rouen at 20 sites in France.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pain, Acute, Emergencies, Morphine
- What is being tested?
- inhaled titration of morphine chlorhydrate and IV titration of morphine chlorhydrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 226 participants
- Where
- 20 sitesFrance
- Study dates
- 19 Sep 2017to 29 Jul 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 21Show fewer
- 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 locations and contacts
20 sites in 1 country.
20 sites in 1 country
France20 sites
CH Agen-Nérac
Agen
CHI Robert Ballanger
Aulnay-sous-Bois
AP-HP
Bobigny
CHU Hôpitaux BORDEAUX
Bordeaux
CHU de Caen
Caen
CHU Gabriel Montpied
Clermont-Ferrand
CH Eure Seine Hôpital d'Evreux
Évreux
CHU Grenoble
Grenoble
GH Le Havre
Le Havre
CH Le Mans
Le Mans
CHRU de Lille
Lille
Hospices civils de Lyon
Lyon
CHU Nice
Nice
Hopital COCHIN
Paris
Hôpital Lariboisière
Paris
La Pitié Salpétrière
Paris
CHU-Hôpitaux de Rouen
Rouen, 76031
Hôpital Bichat-Claude Bernard
Saint-Ouen
Chu Strasbourg
Strasbourg
chu de Toulouse
Toulouse
About this study
Official title: Inhaled Versus Intravenous Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
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).
Read more
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.
- Conditions
- Pain, Acute, Emergencies, Morphine
- Being tested
- inhaled titration of morphine chlorhydrate, IV placebo, Inhaled placebo, IV titration of morphine chlorhydrate
- Medical subject headings
- Acute Pain, Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inhaled titration of morphine chlorhydrateDrug
Also called IV placebo
Patient in arm A will receive 1 to 3 titration
IV placeboDrug
Also called inhaled titration of morphine chlorhydrate
Patient in arm A will receive 1 to 6 injection
Inhaled placeboDevice
Also called IV titration of morphine chlorhydrate
Patient in arm B will receive 1 to 3 titration
IV titration of morphine chlorhydrateDrug
Also called Inhaled placebo
Patient in arm BA will receive 1 to 6 injection
| Study group | Role | What they receive |
|---|---|---|
| inhaled morphine + IV placebo | Experimental | Arm A: inhaled titration of morphine chlorhydrate+ IV placebo Receives: Drug: inhaled titration of morphine chlorhydrate; Drug: IV placebo |
| IV morphine +inhaled placebo | Placebo comparator | Arm B:IV titration of morphine chlorhydrate + inhaled placebo Receives: Device: Inhaled placebo; Drug: IV titration of morphine chlorhydrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1 hour after the initiation of the titration
Secondary outcomes (13)
Evaluate antalgic efficacy criteria
Quantity of morphine administered from the beginning of the titration until the end of the titration
Measured: From the beginning of the titration until the end of the titration- assessed within one day
Evaluate antalgic efficacy criteria
Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained
Measured: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Delay between first administration of Morphine and EVA ≤ 30 or EN ≤ 3 obtained for patient treated only with morphine IV
Measured: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 at the end of titration
Measured: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 at 30 minutes
Measured: 30 minutes after the initiation of the titration
Evaluate antalgic efficacy criteria
Number of patients treated only by exclusive inhalation titration with EVA ≤ 30 or EN ≤ 3
Measured: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Quantity of of co-analgesia administered from the beginning of the titration
Measured: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 after 60 minutes
Measured: 1hour after the initiation of the titration
Evaluate antalgic efficacy criteria
Number of patients with EVA ≤ 30 or EN ≤ 3 after 120 minutes
Measured: 2hours after the initiation of the titration
Assess the feasibility of an aerosol titration (compliance to the protocol)
Number of deviations from protocol
Measured: From the beginning of the titration until the end of the aerosol titration- within one hour after the start of the titration
Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events)
Proportion of Sleepy patients (Ramsay score = 3)
Measured: Until 3hours after the end of the titration
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,
...)
Measured: Until 3hours after the end of the titration
Safety- Proportion of serious adverse events in each arm
Proportion of serious adverse events in each arm
Measured: Until 3hours after the end of the titration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start19 Sep 2017
- Primary completion29 Jul 2022
- Study completion29 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, AcuteStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03257319
- Sponsor's protocol ID
- 2014/0009/HP
- Acronym
- CLIN-AEROMORPH
- Status last verified
- Feb 2026
- First submitted
- 20 Jul 2017
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30975187
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Versus Intravenous Opioid Dosing for the Initial Treatment of Severe Acute Pain in the Emergency Department
- ClinicalTrials.gov ID
- NCT03257319
- Acronym / sponsor ID
- CLIN-AEROMORPH / 2014/0009/HP
- Conditions
- Pain, Acute, Emergencies, Morphine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 19 Sep 2017 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 29 Jul 2022 (actual)
- First posted
- 22 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| inhaled morphine + IV placebo | Experimental | Drug: inhaled titration of morphine chlorhydrate, Drug: IV placeboArm A: inhaled titration of morphine chlorhydrate+ IV placebo |
| IV morphine +inhaled placebo | Placebo comparator | Device: Inhaled placebo, Drug: IV titration of morphine chlorhydrateArm B:IV titration of morphine chlorhydrate + inhaled placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (21 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inhaled titration of morphine chlorhydrateAlso: IV placeboPatient in arm A will receive 1 to 3 titration | Drug | inhaled morphine + IV placebo |
| IV placeboAlso: inhaled titration of morphine chlorhydratePatient in arm A will receive 1 to 6 injection | Drug | inhaled morphine + IV placebo |
| Inhaled placeboAlso: IV titration of morphine chlorhydratePatient in arm B will receive 1 to 3 titration | Device | IV morphine +inhaled placebo |
| IV titration of morphine chlorhydrateAlso: Inhaled placeboPatient in arm BA will receive 1 to 6 injection | Drug | IV morphine +inhaled placebo |
Primary outcome
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
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).
13 secondary outcomes
Evaluate antalgic efficacy criteria
Time frame: From the beginning of the titration until the end of the titration- assessed within one day
Evaluate antalgic efficacy criteria
Time frame: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Time frame: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Time frame: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Time frame: 30 minutes after the initiation of the titration
Evaluate antalgic efficacy criteria
Time frame: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Time frame: From the beginning of the titration until the end of the titration- assessed up to one day
Evaluate antalgic efficacy criteria
Time frame: 1hour after the initiation of the titration
Evaluate antalgic efficacy criteria
Time frame: 2hours after the initiation of the titration
Assess the feasibility of an aerosol titration (compliance to the 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
Safety-Proportion of Sleepy patients (Ramsay score = 3) (adverse events)
Time frame: Until 3hours after the end of the titration
Safety- 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
Safety- Proportion of serious adverse events in each arm
Time frame: Until 3hours after the end of the titration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Derived from this study: PubMed 30975187Lvovschi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing inhaled titration of morphine chlorhydrate and IV titration of morphine chlorhydrate in people with Pain, Acute and Emergencies, run by University Hospital, Rouen at 20 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). (time frame: 1 hour after the initiation of the titration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03257319, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.