ClinicalTrials.gg
RecruitingNCT04576078NefPOUpdated May 14, 2026

Post-operative Analgesic Effect of Oral Nefopam

A Phase 2 interventional study of Oral nefopam and Placebo in Postoperative Pain After a Total Knee Arthroplasty, sponsored by Hospices Civils de Lyon. Recruiting at 1 site in France. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-05-14.

Sponsored by Hospices Civils de Lyon · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Jun 2021; still recruiting 5 years 4 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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).

02

Conditions studied

  • Postoperative Pain After a Total Knee Arthroplasty

Keywords

  • Nefopam
  • Oral
  • postoperative pain
  • hyperalgesia
  • cerebrospinal fluid and plasma concentration
  • total knee arthroplasty
03

In context

Pain, Postoperative

5,640 studies on the registry are indexed under Pain, Postoperative; 1,230 are open to participants now.

This study's planned enrollment of 50 is below the median of 75 across 4,821 interventional studies indexed under Pain, Postoperative.

Browse Pain, Postoperative studies →

Lead sponsor

Hospices Civils de Lyon is the lead sponsor of 1,866 studies on the registry; 448 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

Exclusion criteria

Exclusion Criteria:

  • any for nefopam (known , 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 (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
Terms in these criteria, in plain language(4)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
50 participants (estimated)

Study arms

  • Experimental
    NEFOPAM 60mg PO/ 8 hours

    Oral administration of nefopam 60mg 2 hours before the surgery following by 60mg each 8h for 24h.

    Drug: Oral nefopam

  • Placebo comparator
    Placebo

    Oral administration of a placebo 2 hours before the surgery following by one administration each 8h for 24h.

    Drug: Placebo

Interventions

  • 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.

  • DrugPlacebo

    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

06

What researchers measure

Primary outcomes

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

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

    Time frame: 24 hours after the surgery.

Secondary outcomes

  1. Hyperalgesia - Pressure Pain Threshold

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

    Time frame: 24 hours after the surgery

  2. Hyperalgesia - Punctate Pain Intensity

    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.

    Time frame: 24 hours after the surgery

  3. Hyperalgesia - Allodynia zone

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

    Time frame: 24 hours after the surgery

  4. Pain intensity

    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)

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

  5. Self reported safety outcomes

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

    Time frame: 24 hours after the surgery

  6. Measures Safety outcomes

    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.

    Time frame: 24 hours after the surgery

  7. Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam

    Plasmatic and cerebrospinal fluid concentration of nefopam is measured.

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

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

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

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

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

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

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

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

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

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

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

    Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride is measured.

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

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

    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.

    Time frame: 3 months after the surgery

  13. Persistent postoperative pain - DN4

    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.

    Time frame: 4 months after the surgery

07

Study locations

1 of 1 sites recruiting
  • Département d'Anesthésie Réanimation, Groupement Hospitalier Nord, Hospices Civils de Lyon
    Lyon, Lyon 69004, France
    Recruiting
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 14, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT04576078
Responsible party
Sponsor
First posted
Oct 6, 2020
Start date
Jun 29, 2021
Primary completion
Dec 30, 2026 (estimated)
Completion
May 15, 2027 (estimated)
Last update
May 14, 2026

Study contacts

Frederic AUBRUN, MD/PHD
Contact
Frederic.aubrun@chu-lyon.fr
4 72 07 26 11 ext. +33
Solene PANTEL
Contact
solene.pantel02@chu-lyon.fr
4 26 73 27 25 ext. +33
Frederic AUBRUN, MD/PHD
principal investigator · Département d'Anesthésie Réanimation, Hopital de la Croix Rousse

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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