Opioid-free Analgesia in Intensive Care Unit

Intubation Clinical Trial

— OFICU  

Official title:

Opioid-free Analgesia in Intensive Care Unit: a Prospective, Monocentric, Randomized, Double Blind, Feasability Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05825560
• Other study ID #: LOCAL/2022/RW-01
• Secondary ID: 2022-003273-37
• Status: Recruiting
• Phase: Phase 4
• Start date: May 15, 2023
• Est. completion date: August 15, 2026

Study information

• Verified date: February 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Remy WIDEHEM, Dr.
• Phone: +33 4.66 68 30 50
• Email: remy.widehem[@]chu-nimes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 15, 2026
• Est. primary completion date: May 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• 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).

Related Conditions & MeSH terms

• Intubation

Intervention

Drug:
• OFA multimodal analgesia
Multimodal opioid free analgesia
• Standard multimodal analgesia
Standard remifentanil analgesia

Locations

Country	Name	City	State
France	Remy WIDEHEM	Nîmes	Gard

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Impact of a non-opioid analgesia strategy on morphine savings at D7	Cumulative dose of remifentanil	Day 28
Secondary	Impact of an opioid-free analgesia strategy on sedative consumption	Number of lived days free of remifentanil	Day 28
Secondary	Impact of an opioid-free analgesia strategy on sedative consumption	Daily consumption of sedative drugs from inclusion to D28	Day 28
Secondary	Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation	Number of live days free of mechanical ventilation	Day 28
Secondary	Impact of an opioid-free analgesia strategy on norepinephrine	Number of lived days free of norepinephrine	Day 28
Secondary	Impact of a non-opioid analgesia strategy on organ failure at D28	SOFA Score (Sepsis-related Organ Failure Assessment)	Day 28
Secondary	Impact of a non-opioid analgesia strategy on fluid intake	Daily fuid intake in milliliter	Day 28
Secondary	Impact of a non-opioid analgesia strategy on mental confusion	CAM ICU test	Day 28
Secondary	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	Day 28
Secondary	Impact of a non-opioid analgesia strategy on the incidence of ventilator-associated pneumonia	Presence of pneumonia associated with mechanical ventilation	Day 28
Secondary	Impact of a non-opioid analgesia strategy on extubation failure rates	extubation failure and cause (reintubation within 48 hours of first extubation)	48 hours after extubation
Secondary	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	Day 90
Secondary	Impact of the non-opioid analgesia strategy on vital prognosis at D28 and D90.	Vital status at day 28 and day 90	Day 90
Secondary	Impact of a non-opioid analgesia strategy on morphine dependence at D90	Opioid use at D90	Day 90