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

Official title

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

Overview

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.

Interventions

• 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)
• 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)

Primary outcome measures

• 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). [Time frame: between Day 0 - Hour 0 and Hour 24 post surgery]

Secondary outcome measures (12)

• 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. [Time frame: at PACU, between PACU discharge and Hour 24, at Hour 24 and at Day 5 of hospital discharge]
• Time to return to walking. [Time frame: At Hour 24, at Day 5 or at discharge, whichever came first and at Month 6]
• Time to leave room. [Time frame: At Hour 24, at Day 5 or at discharge, whichever came first and at Month 6]
• Time to climb stairs. [Time frame: At Hour 24, at Day 5 or at discharge, whichever came first and at Month 6]
• Length of stay. [Time frame: At Day 0 - Hour 0 up to Day 5 or at discharge]
• Time to abandon canes/crutches. [Time frame: 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 [Time frame: at Hour 24 and up to day 5]
• Chronic pain at 6 months (at rest and walking) using a standardized phone questionnaire. [Time frame: 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). [Time frame: At Hour 24 and Month 6]
• Incidence of all serious AEs during patient follow-up and non-serious AEs. [Time frame: at Hour 24 and up to day 5]
• Incidence of patients with morphine side effects [Time frame: 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. [Time frame: 5 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

France · 7 centers

• Anaesthesia - Intensive care — Angers
• Anaesthesia - Intensive care — Blois
• Anaesthesia - Intensive care — Chartres
• Anaesthesia - Intensive care — Nantes
• Anaesthesia - Intensive care — Orléans
• Anaesthesia - Intensive care — Poitiers
• Anesthesia - intensive care — Tours

Identifiers

NCT: NCT06349798 · DR200177

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗