Opioid-free Analgesia in Intensive Care Unit

NCT05825560 | Recruiting Phase 4

• 2 other identifiers: LOCAL/2022/RW-012022-003273-37
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Intubation

Keywords

orotracheal intubation; mechanical ventilation; sedation analgesia

Outcome Measures

Primary Outcomes (1)

• 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

  48th hour after randomisation

Secondary Outcomes (14)

• Impact of a non-opioid analgesia strategy on morphine savings at D7

  Day 28

• Impact of an opioid-free analgesia strategy on sedative consumption

  Day 28

• Impact of an opioid-free analgesia strategy on sedative consumption

  Day 28

• Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation

  Day 28

• Impact of an opioid-free analgesia strategy on norepinephrine

  Day 28

Study Arms (2)

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.

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.

Drug: OFA multimodal analgesia

Interventions

OFA multimodal analgesia DRUG

Multimodal opioid free analgesia

OFA Group

Standard multimodal analgesia DRUG

Standard remifentanil analgesia

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patient already involved in a trial that might influence our primary endpoint.
• 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.
• 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).

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

Remy WIDEHEM

Nîmes, Gard, 30029, France

RECRUITING

Related Publications (3)

• 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.

  PMID: 32696016 BACKGROUND

• Devlin 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.

  PMID: 30113379 BACKGROUND

• Widehem 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.

  PMID: 39832962 DERIVED

Central Study Contacts

Remy WIDEHEM, Dr.

CONTACT

+33 4.66 68 30 50; remy.widehem@chu-nimes.fr

Claire ROGER, Dr. PhD

CONTACT

+33 4.66.68.30.50; claire.roger@chu-nimes.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: April 24, 2023
• Study Start: May 15, 2023
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)