Early and Late Effects of Nefopam in Multimodal Analgesia After Total Hip Arthroplasty (NEFARTHRO) (NEFARTHRO)

Early and Late Effects of Nefopam in Multimodal Analgesia After Total Hip Arthroplasty (NEFARTHRO): a Multicentric Randomized Controlled Trial.

NEFARTHRO is a multicentric randomized controlled trial comparing the effects of discontinuous infusions of nefopam (bolus) versus continuous infusion of intravenous nefopam (via an infusion pump) versus placebo on the opioid-request during the first 24 hours following a Total Hip arthroplasty, as part of multimodal analgesia including at least paracetamol and a Non-Steroidal Anti-Inflammatory Drug (NSAID).

The primary endpoint is cumulative morphine consumption for the first postoperative 24 hours, expressed in mg of iv equivalent morphine, including titration in the Post Anesthesia Care Unit (PACU).

Patients will be followed during 6 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Total Hip Arthroplasty
• Intervention / Treatment: Drug: Nefopam; Drug: Nefopam; Drug: NaCl 0.9%

• Study Type: Interventional
• Enrollment (Estimated): 546
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Francis REMERAND, MD PhD; Phone Number: +33 02.47.47.85.51; Email: f.remerand@chu-tours.fr
• Study Contact Backup: Name: Stellina AUGIS; Phone Number: +33 02.47.47.46.38; Email: stellina.augis@chu-tours.fr

Study Locations

• France
  • Angers, France, 49933
    • Anaesthesia - Intensive care
    • Contact: Emmanuel RINEAU, MD; Phone Number: +33 02 41 35 39 51; Email: Emmanuel.Rineau@chu-angers.fr
    • Principal Investigator: Emmanuel RINEAU, MD
  • Blois, France, 41016
    • Anaesthesia - Intensive care
    • Contact: Raphaël DARMON, MD; Phone Number: +33 02 54 55 66 33; Email: darmonr@ch-blois.fr
    • Principal Investigator: Raphaël DARMON, MD
  • Chartres, France, 28018
    • Anaesthesia - Intensive care
    • Contact: Elias CHADDOUK, MD; Phone Number: +33 02 37 30 30 30; Email: echaddouk@ch-chartres.fr
    • Principal Investigator: Elias CHADDOUK, MD
  • Nantes, France, 44000
    • Anaesthesia - Intensive care
    • Contact: Raphaël CINOTTI, MD; Phone Number: +33 02 53 48 22 30; Email: Raphael.CINOTTI@chu-nantes.fr
    • Principal Investigator: Raphaël CINOTTI, MD
  • Orléans, France, 45067
    • Anaesthesia - Intensive care
    • Contact: Léa PARCOT, MD; Phone Number: +33 02 38 22 97 17; Email: lea.pascot@chr-orleans.fr
    • Principal Investigator: Léa PARCOT, MD
  • Poitiers, France, 86021
    • Anaesthesia - Intensive care
    • Contact: Denis FRASCA, MD; Phone Number: +33 05 49 44 38 95; Email: denis.frasca@univ-poitiers.fr
    • Principal Investigator: Denis FRASCA, MD
  • Tours, France, 37044
    • Anesthesia - intensive care
    • Contact: Francis REMERAND, MD; Phone Number: +33 02 47 47 84 80; Email: F.REMERAND@chu-tours.fr
    • Principal Investigator: Francis REMERAND, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient aged ≥ 18 years, fluent in French.
• Planned primary or secondary total hip replacement, regardless of surgical approach or type of prosthesis.
• Receiving paracetamol and ketoprofen postoperatively.
• Under general anesthesia or spinal anesthesia (without intrathecal morphine).
• Participant affiliated to a social security scheme
• Participant's free, informed and written consent

Exclusion Criteria:

• Septic or carcinological surgery
• Allergy to paracetamol, nefopam or NSAIDs
• Angle-closure glaucoma
• Prostate adenoma
• history of convulsion
• Nocturnal pollakiuria in men with more than two risings per night
• Severe hepatic (Child C) or cardiac insufficiency (LVEF < 30%)
• Renal insufficiency with creatinine clearance < 50 mL/ min according to Cockroft's formula
• Active peptic ulcer or history of digestive bleeding or peptic perforation
• Patients with opioid treatment for chronic pain other than coxarthrosis (fentanyl, oral morphine > 50mg/d or equivalent)
• Protected patient: safeguard of justice, guardianship or curatorship
• Incomprehension or inability to use a numerical rating scale or to self-assess/manage pain
• Pregnancy or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group	Drug: NaCl 0.9%; 50 ml of saline, during a 30 min infusion, before end of procedure, followed by a bolus of placebo every 4 hours for 24 hours (6 injections in all) + continuous infusion of placebo (2 mL/h of physiological saline)
Experimental: Nefopam "bolus" group	Drug: Nefopam; 20 mg nefopam in 50 ml of saline, during a 30 min infusion, before end of procedure, then a similer bolus every 4 h for 24 h (6 injections in total) + continuous intravenous infusion of placebo (2 mL/h saline); Drug: Nefopam; 20 mg nefopam in 50 ml of saline, during a 30 min infusion, before end of procedure, then a bolus of placebo every 4 h for 24 h (6 injections in total) + continuous infusion of 100 mg nefopam over 24 h (in 48 mL saline, 2 mL/h)
Experimental: Nefopam "CIVI" group	Drug: Nefopam; 20 mg nefopam in 50 ml of saline, during a 30 min infusion, before end of procedure, then a similer bolus every 4 h for 24 h (6 injections in total) + continuous intravenous infusion of placebo (2 mL/h saline); Drug: Nefopam; 20 mg nefopam in 50 ml of saline, during a 30 min infusion, before end of procedure, then a bolus of placebo every 4 h for 24 h (6 injections in total) + continuous infusion of 100 mg nefopam over 24 h (in 48 mL saline, 2 mL/h)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative morphine consumption from the end of surgery (Day 0 - Hour 0) to the first 24 hours after surgery, expressed in mg of intravenous morphine (including titration in the Post-Anesthesia care Unit PACU).	between Day 0 - Hour 0 and Hour 24 post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum self-assessed pain using the Numeric Rating Scale ranging from 0 (no pain) to 10 (maximum pain) at rest in the PACU, at rest and on walking between PACU discharge and Hour 24, at Hour 24, and at hospital discharge.		at PACU, between PACU discharge and Hour 24, at Hour 24 and at Day 5 of hospital discharge
Time to return to walking.		At Hour 24, at Day 5 or at discharge, whichever came first and at Month 6
Time to leave room.		At Hour 24, at Day 5 or at discharge, whichever came first and at Month 6
Time to climb stairs.		At Hour 24, at Day 5 or at discharge, whichever came first and at Month 6
Length of stay.		At Day 0 - Hour 0 up to Day 5 or at discharge
Time to abandon canes/crutches.		At Hour 24, at Day 5 or at discharge, whichever came first and at Month 6
Opioid analgesic consumption between days 1 and 5 or at hospital discharge		at Hour 24 and up to day 5
Chronic pain at 6 months (at rest and walking) using a standardized phone questionnaire.		At Month 6
Neuropathic pain score (DN2)The DN2 is a simplified version of the DN4, with 7 items: burning, painful cold, electric shocks, tingling, pins and needles, numbness, itching (scored 0=absent, 1=present).		At Hour 24 and Month 6
Incidence of all serious AEs during patient follow-up and non-serious AEs.		at Hour 24 and up to day 5
Incidence of patients with morphine side effects	Incidence of patients with morphine side effects: nausea, vomiting, use of anti-nausea medication, pruritus requiring modification of management, urinary retention, use of urinary antispasmodics or urethral catheterization/suprapubic catheter, or abnormal drowsiness.	at Hour 24 and up to day 5
Financial impact of spreading the recommended strategy following the results of the clinical study, estimated per year and over a 5-year period, from the point of view of the French Health Insurance and from the hospital perspective.	These financial impacts will be estimated using budget impact models.	5 years

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Principal Investigator: Francis REMERAND, MD PhD, Chru De Tours

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Nefopam
• Other Study ID Numbers: DR200177

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
• product manufactured in and exported from the U.S.: No