Comparison of an Opioid-Free Anesthesia Protocol Versus Standard Practices on Early and Late Post-operative Recovery (SOFA)

Opioid-Free Anesthesia (OFA) is an anesthesia protocol that does not use morphine, and is increasingly used routinely. Indeed, this protocol would theoretically allow a better post-operative analgesic control, a lower incidence of post-operative complications (e.g. post-operative nausea and vomiting). In the end, it would also allow a better overall post-operative recovery and a decrease in the incidence of chronic post-operative pain.

Nevertheless, the literature is poor on this issue and no randomized controlled study has evaluated the effect of the use of this type of anesthesia protocol on postoperative recovery.

Study Overview

• Status: Recruiting
• Conditions: Anesthesia; Post-Op Complication; Opioid Analgesic Adverse Reaction; Anesthesia; Adverse Effect
• Intervention / Treatment: Drug: Opioid Free Anaesthesia protocol; Drug: standard practice protocol based on the use of opioids (sufentanil or remifentanil)

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Béatrice Gable; Phone Number: +33 241356825; Email: begable@chu-angers.fr
• Study Contact Backup: Name: Maxime Léger, MD; Phone Number: +33 241353635; Email: maxime.leger@chu-angers.fr

Study Locations

• France
  • Angers, France, 49000
    • Recruiting
    • University Hospital of Angers
    • Contact: Maxime Léger, MD; Phone Number: +33 683134722; Email: maxime.leger@chu-angers.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years
• Surgery lasting more than 90 minutes with planned use of morphine analgesics during post-operative hospitalization (outside the PACU stay),
• ENT surgery, plastic and reconstructive surgery, digestive and visceral surgery, urological surgery and gynecological surgery,
• Surgery that does not involve any bone procedure,
• Written consent of the patient,
• French-speaking patient, able to understand and answer a questionnaire,
• Social security affiliation

Exclusion Criteria:

• Pregnant, breastfeeding or parturient woman,
• Person deprived of liberty by judicial or administrative decision,
• A person who is subject to a legal protection measure,
• Person unable to express consent,
• BMI < 18 and > 39 kg/m2,
• Drug contraindications, in particular hypersensitivity to the active substances of one of the study drugs (in particular lidocaine hydrochloride or amide- or clonidine-linked local anaesthetics) or to one of the excipients,
• Porphyria,
• Heart failure or unstable coronary artery disease,
• bradyarrhythmia due to sinus node disease or conduction clock, or Adam-Stock's syndrome, not fitted,
• Hepatocellular insufficiency with TP < or =50%,
• Chronic renal failure with glomerular filtration < 60 ml/min.
• Long-term treatment with Imipraminics, Neuroleptics, Baclofen, and all other molecules at risk of QT prolongation,
• Uncontrolled epilepsy,
• Chronic treatment with beta-blockers,
• Need for induction in fast sequence,
• Severe psychiatric or cognitive disorder that interferes with the evaluation through questionnaires.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Opioid free anesthesia (OFA) protocol	Drug: Opioid Free Anaesthesia protocol; The OFA protocol begins with a systematic preoperative premedication with clonidine, continues with an adapted intraoperative management without opioid administration, but associating several molecules (clonidine, magnesium, lidocaine, ketamine) and ends with a continued administration of xylocaine up to 1 hour postoperatively in PACU. The use of an opioid in preoperative or intraoperative phases is considered as a deviation from the protocol. To these different molecules, the use of hypnotic molecules left to the choice of the practitioner and a curare will be systematically associated.
SHAM_COMPARATOR: standard practice protocol based on the use of opioids (sufentanil or remifentanil)	Drug: standard practice protocol based on the use of opioids (sufentanil or remifentanil); Standard anesthetic practices can be summed up as the combination of a hypnotic, a morphinic (sufentanil or remifentanil) and a curare. The use of ketamine is allowed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FQoR-15 score at 24 hours	Value of the French Quality of Recovery-15 score (minimum value of 0 and maximum value of 150, with a higher score for a better outcome). The QoR-15 questionnaires will be completed by the patient himself whenever possible, who could be helped by a nurse blinded to the assignment group, or by phone if the patient has returned home.	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FQoR-15 score at 48 and 72 hours	Value of the French Quality of Recovery-15 score (minimum value of 0 and maximum value of 150, with a higher score for a better outcome). The QoR-15 questionnaires will be completed by the patient himself whenever possible, who could be helped by a nurse blinded to the assignment group, or by phone if the patient has returned home.	48 and 72 hours after surgery
Pain on effort at 6, 12, 24, 48 and 72 hours	Pain evaluated via a 11-item analogue scale (from 0 to 10, with 10 for the worst pain) assessed by a blinded nurse.	6, 12, 24, 48 and 72 hours after surgery
Opioid consumption	Amount of opioid consumption in the 7 days, assessed by a blinded investigator.	7 days
Proportion of patient with at least one POMS complication at 24, 48 and 72 hours	POMS complication as described in the Post-operative Morbidity Survey, assessed by a blinded investigator.	24, 48 and 72 hours
Surgeon satisfaction at day 1	satisfaction concerning the protocole evaluated via a 11-item analogue scale (from 0 to 10, with 10 for the worst pain)	day 1
anesthesiologist satisfaction at day 1	satisfaction concerning the protocole evaluated via a 11-item analogue scale (from 0 to 10, with 10 for the worst pain)	day 1
Incidence of hemodynamic, rhythmic and allergic complications at day 1	Hemodynamic tolerance: the need to introduce catecholamines intraoperatively, or the need to stop one of the treatments in the protocol for hemodynamic reasons, Rhythmic tolerance: episode of extreme bradycardia < 35 bpm or tachycardia > 140 bpm for more than 30 seconds, The occurrence of a hypersensitivity reaction or other adverse events attributable to the anesthesia protocol. The complications are collected by the anesthesia team.	day 1
Proportion of patients with chronic pain at 3 months	Proportion of patients with chronic pain at 3 months detecting with brief pain inventory, assessed by a blinded investigator.	3 months
Quality of life measured from EQ VAS (EQ-5D-3L)	The Quality of life is evaluated via EQ VAS (derivating from the 5-level EQ-5D version (EQ-5D-3L), by a blinded assessor. The value from this scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine'. The scale is rated from 0 to 100.	3 months
Proportion of neuropathic pain at 3 months	The proportion of patients reporting neuropathic pain is defined by the DN4 questionnaire by a phone call with a blinded investigator. If the score is equal to or greater than 4/10, we define the presence of neuropathic pain.	3 months
Proportion of respect of the allocated anesthesia protocol	Respect of the allocated protocol by the anesthesia team: OFA protocol will be considered complete if at least two of the following drugs are used between ketamine, lidocaine, clonidine and magnesium sulfate, and if no intraoperative opioids are used; the standard group will be considered complete if lidocaine, clonidine or magnesium sulfate are not used intra-operatively. This outcome is collected by one of the investigator.	24 hours after surgery

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Publications and helpful links

General Publications

• Mauermann E, Ruppen W, Bandschapp O. Different protocols used today to achieve total opioid-free general anesthesia without locoregional blocks. Best Pract Res Clin Anaesthesiol. 2017 Dec;31(4):533-545. doi: 10.1016/j.bpa.2017.11.003. Epub 2017 Nov 24.
• Leger M, Campfort M, Cayla C, Parot-Schinkel E, Lasocki S, Rineau E. Validation of an alternative French version of the Quality of Recovery-15 Score: the FQoR-15. Br J Anaesth. 2020 Oct;125(4):e345-e347. doi: 10.1016/j.bja.2020.05.052. Epub 2020 Jul 9. No abstract available.
• Leger M, Pessiot-Royer S, Perrault T, Parot-Schinkel E, Costerousse F, Rineau E, Lasocki S. The effect of opioid-free anesthesia protocol on the early quality of recovery after major surgery (SOFA trial): study protocol for a prospective, monocentric, randomized, single-blinded trial. Trials. 2021 Nov 27;22(1):855. doi: 10.1186/s13063-021-05829-x.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 12, 2021
• Primary Completion (ANTICIPATED): November 1, 2022
• Study Completion (ANTICIPATED): May 1, 2023

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (ACTUAL): March 15, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 14, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Anesthesia; Quality of recovery; patient centered outcome
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Narcotics; Adjuvants, Anesthesia; Remifentanil; Analgesics, Opioid; Sufentanil
• Other Study ID Numbers: SOFA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No