IntubationPhase 4OFICUNCT05825560
Opioid-free Analgesia in Intensive Care Unit
A Phase 4 study testing OFA multimodal analgesia and Standard multimodal analgesia in people with Intubation, run by Centre Hospitalier Universitaire de Nīmes at 1 site in France.
Trial summary
ICU patients experience moderate to severe pain. Studies and guidelines point out the benefits of multimodal analgesia on pain control, opioid spare and on lowering its adverse effects. However, no recommendation about drugs or protocol has been formulated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intubation
- What is being tested?
- OFA multimodal analgesia and Standard multimodal analgesia
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 15 May 2023to 16 Jun 2026
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient hospitalized in ICU and requiring sedation-analgesia for mechanical ventilation.
- Patient undergoing mechanical ventilation for more than 2 hours and less than 24 hours.
- Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure.
- Patient affiliated to the French Government Public Health Insurance.
- Patient over 18 years old.
Who cannot join
- Patient already involved in a trial that might influence our primary endpoint.
- Patient in exclusion-period determined by another trial or study.
- Patient who is likely to be requiring less than 48 hours of mechanical ventilation.
- Patient with contraindication or allergies to at least one of the following medication : paracetamol, nefopam, tramadol, ketamine, remifentanil.
- Patient with hepatic insufficiency (defined as PT < 50%).
- Parturient or breast-feeding patient.
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- Patient suffering from moderate to severe Acute Respiratory Distress Syndrome (ARDS), with decreased PaO2/FiO2 ratio under 150mmHg after respiratory optimization (courant volume 6mL/kg and PEEP > 5mbar).
- Patient requiring curare treatment.
- Patients with an indication for locoregional analgesia prior to extubation (perineural sealing, epidural analgesia).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Opioid-free Analgesia in Intensive Care Unit: a Prospective, Monocentric, Randomized, Double Blind, Feasability Clinical Trial
ICU patients experience moderate to severe pain. Studies and guidelines point out the benefits of multimodal analgesia on pain control, opioid spare and on lowering its adverse effects. However, no recommendation about drugs or protocol has been formulated. In our study, investigators studied the feasibility and the impact on Remifentanil spare of a standardized protocol using multimodal analgesia (Paracetamol, Nefopam, Tramadol, Ketamine, Remifentanil) compared to the standard-of-care strategy using Paracetamol and Remifentanil. The investigators conducted a prospective, ''proof of concept'', randomized, double-blind, parallel group, placebo-controlled trial. The investigators studied multimodal analgesia versus standard-of-care in ICU patients requiring sedation-analgesia for invasive mechanical ventilation.The investigators hypothesized that Remifentanil consumption decrease by 15% with the use of a standardized multimodal analgesia strategy
Read the detailed description
ICU patients requiring sedation-analgesia for mechanical ventilation for at least 48 hours are randomized in 2 parallel groups : control arm using ''standard of care'' analgesia (Paracetamol and Remifentanil), and interventional arm using multimodal analgesia at different level according to pain accessed by BPS (Step 1 : Paracetamol, Nefopam, Tramadol, Step 2 : Ketamine, Step 3 : Remifentanil). Sedation drugs are standard of care (Propofol and Midazolam if Propofol isn't enough) to obtain prescribed sedation accessed by RASS. Double-bling is kept for 72 hours until the primary outcome is obtained.
The investigators hypothesize a 15% reduction of Remifentanil consumption in the interventional group.
- Conditions
- Intubation
- Being tested
- OFA multimodal analgesia, Standard multimodal analgesia
- Keywords
- orotracheal intubation, mechanical ventilation, sedation analgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OFA multimodal analgesiaDrug
Multimodal opioid free analgesia
Standard multimodal analgesiaDrug
Standard remifentanil analgesia
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Analgesia combines paracetamol (1g every 6 to 8 hours according to age and weight recommendations) and remifentanil, adapted according to a tiered administration system depending on the Behavior Pain Scale (BPS) and the theoretical ideal weight. Remifentanil doses are adjusted so that the patient has a BPS score of 4 or less. Reassessment of analgesia will be carried out every 30 minutes until analgesic adaptation is complete, then every 2 hours as is usually done in our department.
If the BPS is less than or equal to 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped.
After the sedation balance phase, the patient's BPS will be assessed every 2 hours. Receives: Drug: Standard multimodal analgesia |
| OFA Group | Experimental | A fixed combination of nefopam and tramadol will be initiated at daily doses. An initial dose of 50mg tramadol and 20mg nefopam IV over 30 min. will be administered. Reassessment of analgesia will be performed every 30 min. for two hour and then every 2 hours.
* If BPS is > 4, administration of ketamine with an initial bolus of 0.15mg/kg followed by continuous administration at a dose of 0.15mg/kg/hour.
* If the BPS is < 4, remifentanil is introduced at the minimum effective dose, in a stepwise fashion according to the theoretical ideal weight
* In the event of maximum pain requiring the full range of therapies in the algorithm the total dose of tramadol will be 450mg/day and nefopam 120mg/day, in accordance with summaries of product characteristics.
* If the BPS < or = 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped, according to the following scheme: remifentanil, ketamine, tramadol and then nefopam. Receives: Drug: OFA multimodal analgesia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daily remifentanil consumption (after randomisation)
daily consumption of remifentanil between the 24th hour and the 48th hour after randomisation of patients admitted to the ICU and requiring at least 48 hours of mechanical ventilation
Measured: 48th hour after randomisation
Secondary outcomes (14)
Impact of a non-opioid analgesia strategy on morphine savings at D7
Cumulative dose of remifentanil
Measured: Day 28
Impact of an opioid-free analgesia strategy on sedative consumption
Number of lived days free of remifentanil
Measured: Day 28
Impact of an opioid-free analgesia strategy on sedative consumption
Daily consumption of sedative drugs from inclusion to D28
Measured: Day 28
Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation
Number of live days free of mechanical ventilation
Measured: Day 28
Impact of an opioid-free analgesia strategy on norepinephrine
Number of lived days free of norepinephrine
Measured: Day 28
Impact of a non-opioid analgesia strategy on organ failure at D28
SOFA Score (Sepsis-related Organ Failure Assessment)
Measured: Day 28
Impact of a non-opioid analgesia strategy on fluid intake
Daily fuid intake in milliliter
Measured: Day 28
Impact of a non-opioid analgesia strategy on mental confusion
CAM ICU test
Measured: Day 28
Impact of a non-opioid analgesia strategy on the occurrence of morphine-related adverse events
Presence of one or more events of special interest or expected adverse events: constipation, bradycardia, bladder globe, nausea, vomiting, liver disturbance, serotonin syndrome
Measured: Day 28
Impact of a non-opioid analgesia strategy on the incidence of ventilator-associated pneumonia
Presence of pneumonia associated with mechanical ventilation
Measured: Day 28
Impact of a non-opioid analgesia strategy on extubation failure rates
extubation failure and cause (reintubation within 48 hours of first extubation)
Measured: 48 hours after extubation
Impact of a non-opioid analgesia strategy onICU and hospital length of stay
Length of stay in the intensive care unit and in the hospital
Measured: Day 90
Impact of the non-opioid analgesia strategy on vital prognosis at D28 and D90.
Vital status at day 28 and day 90
Measured: Day 90
Impact of a non-opioid analgesia strategy on morphine dependence at D90
Opioid use at D90
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2023
- Study start15 May 2023
- Primary completion16 Jun 2026
- Study completion16 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for IntubationStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NīmesThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nīmes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05825560
- Sponsor's protocol ID
- LOCAL/2022/RW-01
- Other IDs
- 2022-003273-37
- Acronym
- OFICU
- Status last verified
- Jun 2026
- First submitted
- 11 Apr 2023
- Last updated
- 1 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wheeler KE, Grilli R, Centofanti JE, Martin J, Gelinas C, Szumita PM, Devlin JW, Chanques G, Alhazzani W, Skrobik Y, Kho ME, Nunnally ME, Gagarine A, Ergan BA, Fernando S, Price C, Lewin J, Rochwerg B. Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis. Crit Care Explor. 2020 Jul 6;2(7):e0157. doi: 10.1097/CCE.0000000000000157. eCollection 2020 Jul.
PubMed 32696016Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.
PubMed 30113379Widehem R, Nicolet C, Delannoy V, Barthelemi L, Soulairol I, Lefrant JY, Mura T, Roger C. Effect of a multimodal analgesia strategy on remifentanil daily consumption in mechanically ventilated adult ICU patients: study protocol for a randomised, placebo-controlled, double-blind, parallel-group clinical trial. BMJ Open. 2025 Jan 20;15(1):e090396. doi: 10.1136/bmjopen-2024-090396.
PubMed 39832962
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Opioid-free Analgesia in Intensive Care Unit: a Prospective, Monocentric, Randomized, Double Blind, Feasability Clinical Trial
- ClinicalTrials.gov ID
- NCT05825560
- Acronym / sponsor ID
- OFICU / LOCAL/2022/RW-01
- Conditions
- Intubation
- Keywords
- orotracheal intubation, mechanical ventilation, sedation analgesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NīmesUniversity, hospital or other
- Study start
- 15 May 2023 (actual)
- Primary completion
- 16 Jun 2026 (actual)
- Study completion
- 16 Jun 2026 (actual)
- First posted
- 24 Apr 2023 (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.
ICU patients experience moderate to severe pain. Studies and guidelines point out the benefits of multimodal analgesia on pain control, opioid spare and on lowering its adverse effects. However, no recommendation about drugs or protocol has been formulated. In our study, investigators studied the feasibility and the impact on Remifentanil spare of a standardized protocol using multimodal analgesia (Paracetamol, Nefopam, Tramadol, Ketamine, Remifentanil) compared to the standard-of-care strategy using Paracetamol and Remifentanil. The investigators conducted a prospective, ''proof of concept'', randomized, double-blind, parallel group, placebo-controlled trial. The investigators studied multimodal analgesia versus standard-of-care in ICU patients requiring sedation-analgesia for invasive mechanical ventilation.The investigators hypothesized that Remifentanil consumption decrease by 15% with the use of a standardized multimodal analgesia strategy
Detailed description
ICU patients requiring sedation-analgesia for mechanical ventilation for at least 48 hours are randomized in 2 parallel groups : control arm using ''standard of care'' analgesia (Paracetamol and Remifentanil), and interventional arm using multimodal analgesia at different level according to pain accessed by BPS (Step 1 : Paracetamol, Nefopam, Tramadol, Step 2 : Ketamine, Step 3 : Remifentanil). Sedation drugs are standard of care (Propofol and Midazolam if Propofol isn't enough) to obtain prescribed sedation accessed by RASS. Double-bling is kept for 72 hours until the primary outcome is obtained.
The investigators hypothesize a 15% reduction of Remifentanil consumption in the interventional group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Drug: Standard multimodal analgesiaAnalgesia combines paracetamol (1g every 6 to 8 hours according to age and weight recommendations) and remifentanil, adapted according to a tiered administration system depending on the Behavior Pain Scale (BPS) and the theoretical ideal weight. Remifentanil doses are adjusted so that the patient has a BPS score of 4 or less. Reassessment of analgesia will be carried out every 30 minutes until analgesic adaptation is complete, then every 2 hours as is usually done in our department. If the BPS is less than or equal to 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped. After the sedation balance phase, the patient's BPS will be assessed every 2 hours. |
| OFA Group | Experimental | Drug: OFA multimodal analgesiaA fixed combination of nefopam and tramadol will be initiated at daily doses. An initial dose of 50mg tramadol and 20mg nefopam IV over 30 min. will be administered. Reassessment of analgesia will be performed every 30 min. for two hour and then every 2 hours. * If BPS is > 4, administration of ketamine with an initial bolus of 0.15mg/kg followed by continuous administration at a dose of 0.15mg/kg/hour. * If the BPS is < 4, remifentanil is introduced at the minimum effective dose, in a stepwise fashion according to the theoretical ideal weight * In the event of maximum pain requiring the full range of therapies in the algorithm the total dose of tramadol will be 450mg/day and nefopam 120mg/day, in accordance with summaries of product characteristics. * If the BPS < or = 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped, according to the following scheme: remifentanil, ketamine, tramadol and then nefopam. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patient hospitalized in ICU and requiring sedation-analgesia for mechanical ventilation.
- Patient undergoing mechanical ventilation for more than 2 hours and less than 24 hours.
- Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure.
- Patient affiliated to the French Government Public Health Insurance.
- Patient over 18 years old.
Key exclusion criteria (9 listed)
- Patient already involved in a trial that might influence our primary endpoint.
- Patient in exclusion-period determined by another trial or study.
- Patient who is likely to be requiring less than 48 hours of mechanical ventilation.
- Patient with contraindication or allergies to at least one of the following medication : paracetamol, nefopam, tramadol, ketamine, remifentanil.
- Patient with hepatic insufficiency (defined as PT < 50%).
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 |
|---|---|---|
| OFA multimodal analgesiaMultimodal opioid free analgesia | Drug | OFA Group |
| Standard multimodal analgesiaStandard remifentanil analgesia | Drug | Control group |
Primary outcome
Daily remifentanil consumption (after randomisation)
Time frame: 48th hour after randomisation
daily consumption of remifentanil between the 24th hour and the 48th hour after randomisation of patients admitted to the ICU and requiring at least 48 hours of mechanical ventilation
14 secondary outcomes
Impact of a non-opioid analgesia strategy on morphine savings at D7
Time frame: Day 28
Impact of an opioid-free analgesia strategy on sedative consumption
Time frame: Day 28
Impact of an opioid-free analgesia strategy on sedative consumption
Time frame: Day 28
Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation
Time frame: Day 28
Impact of an opioid-free analgesia strategy on norepinephrine
Time frame: Day 28
Impact of a non-opioid analgesia strategy on organ failure at D28
Time frame: Day 28
Impact of a non-opioid analgesia strategy on fluid intake
Time frame: Day 28
Impact of a non-opioid analgesia strategy on mental confusion
Time frame: Day 28
Impact of a non-opioid analgesia strategy on the occurrence of morphine-related adverse events
Time frame: Day 28
Impact of a non-opioid analgesia strategy on the incidence of ventilator-associated pneumonia
Time frame: Day 28
Impact of a non-opioid analgesia strategy on extubation failure rates
Time frame: 48 hours after extubation
Impact of a non-opioid analgesia strategy onICU and hospital length of stay
Time frame: Day 90
Impact of the non-opioid analgesia strategy on vital prognosis at D28 and D90.
Time frame: Day 90
Impact of a non-opioid analgesia strategy on morphine dependence at D90
Time frame: Day 90
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 1 Jul 2026.
- Background: PubMed 32696016Wheeler KE, Grilli R, Centofanti JE, Martin J, Gelinas C, Szumita PM, Devlin JW, Chanques G, Alhazzani W, Skrobik Y, Kho ME, Nunnally ME, Gagarine A, Ergan BA, Fernando S, Price C, Lewin J, Rochwerg B. Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis. Crit Care Explor. 2020 Jul 6;2(7):e0157. doi: 10.1097/CCE.0000000000000157. eCollection 2020 Jul.
- Background: PubMed 30113379Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.
- Derived from this study: PubMed 39832962Widehem R, Nicolet C, Delannoy V, Barthelemi L, Soulairol I, Lefrant JY, Mura T, Roger C. Effect of a multimodal analgesia strategy on remifentanil daily consumption in mechanically ventilated adult ICU patients: study protocol for a randomised, placebo-controlled, double-blind, parallel-group clinical trial. BMJ Open. 2025 Jan 20;15(1):e090396. doi: 10.1136/bmjopen-2024-090396.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing OFA multimodal analgesia and Standard multimodal analgesia in people with Intubation, run by Centre Hospitalier Universitaire de Nīmes at 1 site 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 5 inclusion and 9 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 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Daily remifentanil consumption (after randomisation) (time frame: 48th hour after randomisation). 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 NCT05825560, which also lists 3 linked publications.
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 1 Jul 2026.