Postoperative Pain After a Total Knee ArthroplastyPhase 2NefPONCT04576078
Post-operative Analgesic Effect of Oral Nefopam
A Phase 2 study testing Oral nefopam in people with Postoperative Pain After a Total Knee Arthroplasty, run by Hospices Civils de Lyon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Postoperative Pain After a Total Knee Arthroplasty
- What is being tested?
- Oral nefopam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 29 Jun 2021to 15 May 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Département d'Anesthésie Réanimation, Groupement Hospitalier Nord, Hospices Civils de Lyon
Lyon, Lyon, 69004
Frédéric AUBRUN, MD-PhD, 04 72 07 26 11 ext. +33, frederic.aubrun@chu-lyon.fr
Solène PANTEL, 04 26 73 27 25 ext. +33, solene.pantel02@chu-lyon.fr
About this study
Official title: Postoperative Analgesic Effect of Orally Administrated Nefopam After a Total Knee Arthroplasty: a Randomized Controlled Trial
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).
- Being tested
- Oral nefopam, Placebo
- Keywords
- Nefopam, Oral, postoperative pain, hyperalgesia, cerebrospinal fluid and plasma concentration, total knee arthroplasty
- Medical subject headings
- Pain, Postoperative, Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral nefopamDrug
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.
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| NEFOPAM 60mg PO/ 8 hours | Experimental | Oral administration of nefopam 60mg 2 hours before the surgery following by 60mg each 8h for 24h. Receives: Drug: Oral nefopam |
| Placebo | Placebo comparator | Oral administration of a placebo 2 hours before the surgery following by one administration each 8h for 24h. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 24 hours after the surgery.
Secondary outcomes (13)
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.
Measured: 24 hours after the surgery
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.
Measured: 24 hours after the surgery
Hyperalgesia - Allodynia zone
The extension of allodynia around the wound is measured using a calibrated brush (100 mNewton) 24 hours after incision.
Measured: 24 hours after the surgery
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)
Measured: 24 hours after the surgery and 3 months after the surgery
Self reported safety outcomes
Nausea and vomiting, unusual sweating, drowsiness, hallucinations, nightmares, palpitations, irritability
Measured: 24 hours after the surgery
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.
Measured: 24 hours after the surgery
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam
Plasmatic and cerebrospinal fluid concentration of nefopam is measured.
Measured: 2 hours after the first oral administration of nefopam or Placebo.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide
Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide is measured.
Measured: 2 hours after the first oral administration of nefopam or Placebo.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde
Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde is measured.
Measured: 2 hours after the first oral administration of nefopam or Placebo.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl
Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl is measured.
Measured: 2 hours after the first oral administration of nefopam or Placebo.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride
Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride is measured.
Measured: 2 hours after the first oral administration of nefopam or Placebo.
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.
Measured: 3 months after the surgery
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.
Measured: 4 months after the surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2020
- Study start29 Jun 2021
- Primary completion30 Dec 2026 (estimated)
- Study completion15 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative Pain After a Total Knee ArthroplastyStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frederic AUBRUN, MD/PHD, Principal investigator, Département d'Anesthésie Réanimation, Hopital de la Croix Rousse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04576078
- Sponsor's protocol ID
- 69HCL20_0111
- Other IDs
- 2020-002955-40
- Acronym
- NefPO
- Status last verified
- May 2026
- First submitted
- 29 Sep 2020
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No