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NCT Number: NCT04576078

Post-operative Analgesic Effect of Oral Nefopam

Primary knee arthroplasty by total prosthesis is a painful surgery, performed on patients with advanced gonarthrosis (stage III), thus already presenting hyperalgesia and hyperalgesia and allodynia. This terrain makes the risk of postoperative hyperalgesia but also of persistent postoperative risk of persistent post-surgical pain.

Nefopam is a non-opioid centrally acting analgesic drug used as a part of multimodal analgesia. The opioid-sparing effect of nefopam is still controversial across various surgical procedures. In France nefopam is only available as a parenteral formulation; however it is often administered orally. There is currently no study addressing the efficacy of oral nefopam for the postoperative pain management including pain prevention.

The investigators conduct a prospective, double-blinded randomized controlled study with the main objective to examine the effect of perioperative orally administered nefopam on postoperative pain after a total knee arthroplasty. Secondary objectives include the quantification of wound allodynia, analysis of adverse events, clinical outcomes, and a pharmacokinetic study of orally given nefopam (plasma and cerebrospinal fluid dosage).

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Key information

Conditions

Postoperative Pain After a Total Knee Arthroplasty Hyperalgesia Nervous System Diseases Neurologic Manifestations Pain Pain, Postoperative Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Sensation Disorders Signs and Symptoms Somatosensory Disorders

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Département d'Anesthésie Réanimation, Groupement Hospitalier Nord, Hospices Civils de Lyon

Lyon, 69004, France

Location status: Recruiting

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • adult patients scheduled for a total knee arthroplasty under spinal anesthesia at the Hopital de la Croix Rousse, Hospice Civils de Lyon, France.
  • ASA (American Society of Anesthesiology) class between 1 et 3.
  • written informed consent

Exclusion criteria

  • any contraindication for nefopam (known hypersensitivity, past medical history of seizures, urinary retention, benign prostate hyperplasia, angle glaucoma, ischemic cardiomyopathy waiting for revascularization, atrial fibrillation)
  • medical conditions known to influence the pharmacokinetics of nefopam (chronic kidney failure with Glomerular Filtration Rate (GFR) <30mL/min/1,73m2, liver failure, current treatment with rifampicin, carbamazepine, azoles fungicides, macrolides)
  • current treatment with benzodiazepines, anxiolytics, antidepressants, histamine H1 antagonists, neuroleptics, baclofen, thalidomide, barbiturates
  • medical history of gastric or esophageal surgery.
  • phenylketonuria
  • pregnancy or breastfeeding
  • past use of oral nefopam

Treatment and study plan

Oral nefopam

Drug

Oral administration of nefopam 60mg 2 hours before the surgery following by 60mg each 8h for 24h. Oral nefopam is prepared ex-tempore from the intravenous formulation adding a taste masking compound by a non-caring nurse following detailed instructions.

Placebo

Drug

Oral administration of a placebo 2 hours before the surgery following by one administration each 8h for 24h. Oral placebo is prepared ex-tempore with a taste masking compound by a non-charge nurse following detailed instructions

Primary outcomes

  1. Total morphine consumption within 24h after the surgery.

    Time frame: 24 hours after the surgery.

    Total dose of morphine consumed in 24h frame by a patient (PCA and/or additional morphine administration - parenteral or oral)

Secondary outcomes

  1. Hyperalgesia - Pressure Pain Threshold

    Time frame: 24 hours after the surgery

    The pressure pain threshold is determined using a Von Frey monofilaments on both (operated and contralateral) knees 24 hours after incision.

  2. Hyperalgesia - Punctate Pain Intensity

    Time frame: 24 hours after the surgery

    The Punctuate pain intensity is determined using a Von Frey monofilament n°5,88 (60 g/mm2) and a pain scale (0 = no pain, 10 = the worst pain), on both the operated knee and the contralateral knee 24 hours after incision.

  3. Hyperalgesia - Allodynia zone

    Time frame: 24 hours after the surgery

    The extension of allodynia around the wound is measured using a calibrated brush (100 mNewton) 24 hours after incision.

  4. Pain intensity

    Time frame: 24 hours after the surgery and 3 months after the surgery

    Self-reported pain intensity at rest and while moving the operated leg. Each item is scored on a scale ranging from 0 to 10 (0 = no pain, 10 = the worst pain)

  5. Self reported safety outcomes

    Time frame: 24 hours after the surgery

    Nausea and vomiting, unusual sweating, drowsiness, hallucinations, nightmares, palpitations, irritability

  6. Measures Safety outcomes

    Time frame: 24 hours after the surgery

    The incidence of acute urinary retention, and mean cardiac frequency (calculated from the recorded cardiac frequency 3 times a day) are recorded, confusion, acute angle glaucoma.

  7. Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam

    Time frame: 2 hours after the first oral administration of nefopam or Placebo.

    Plasmatic and cerebrospinal fluid concentration of nefopam is measured.

  8. Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide

    Time frame: 2 hours after the first oral administration of nefopam or Placebo.

    Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide is measured.

  9. Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde

    Time frame: 2 hours after the first oral administration of nefopam or Placebo.

    Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde is measured.

  10. Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl

    Time frame: 2 hours after the first oral administration of nefopam or Placebo.

    Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl is measured.

  11. Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride

    Time frame: 2 hours after the first oral administration of nefopam or Placebo.

    Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride is measured.

  12. Persistent postoperative pain - DN4 (or DN2 by phone)

    Time frame: 3 months after the surgery

    The DN4 questionnaire (or DN2 questionnaire if the visit is realized by phone) ("Douleurs Neuropathiques 4/2" = Neuropathic pain 4/2 in french) is recorded to investigate persistent postoperative pain defined as pain on the operated knee 3 months after the surgery.

  13. Persistent postoperative pain - DN4

    Time frame: 4 months after the surgery

    The DN2 questionnaire ("Douleurs Neuropathiques 2" = Neuropathic pain 2 in french, abbreviated DN4 questionnaire) is recorded by phone if the 3 months visit is realized out of time. If the score is positive (>=3), the DN4 is recorded at hospital within 2 weeks post the 3 months visit.

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Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

Postoperative Analgesic Effect of Orally Administrated Nefopam After a Total Knee Arthroplasty: a Randomized Controlled Trial

Acronym: NefPO

Important dates

Study start
2021
Primary completion
2026
Study completion
2027
First posted
Oct 6, 2020
Registry last updated
May 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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