Post-operative Analgesic Effect of Oral Nefopam

Phase 2

Recruiting

• Conditions: Postoperative Pain After a Total Knee Arthroplasty
• Interventions: Drug: Oral nefopam; Drug: Placebo

• Registration Number: NCT04576078
• Lead Sponsor: Hospices Civils de Lyon

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-29
• Study First Submitted QC: 2020-09-29
• Study First Posted: 2020-10-06
• Study Start: 2021-06-29
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-19
• Last Update Posted: 2024-04-22
• Primary Completion: 2026-06-30
• Study Completion: 2026-11-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NEFOPAM 60mg PO/ 8 hours	Oral nefopam	Oral administration of nefopam 60mg 2 hours before the surgery following by 60mg each 8h for 24h.
Placebo	Placebo	Oral administration of a placebo 2 hours before the surgery following by one administration each 8h for 24h.

Primary Outcome Measures

Name	Time	Method
Total morphine consumption within 24h after the surgery.	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 Outcome Measures

Name	Time	Method
Hyperalgesia - Pressure Pain Threshold	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.
Persistent postoperative pain - DN4 (or DN2 by phone)	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.
Measures Safety outcomes	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.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide	2 hours after the first oral administration of nefopam or Placebo.	Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide is measured.
Hyperalgesia - Punctate Pain Intensity	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.
Pain intensity	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)
Self reported safety outcomes	24 hours after the surgery	Nausea and vomiting, unusual sweating, drowsiness, hallucinations, nightmares, palpitations, irritability
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam	2 hours after the first oral administration of nefopam or Placebo.	Plasmatic and cerebrospinal fluid concentration of nefopam is measured.
Hyperalgesia - Allodynia zone	24 hours after the surgery	The extension of allodynia around the wound is measured using a calibrated brush (100 mNewton) 24 hours after incision.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl	2 hours after the first oral administration of nefopam or Placebo.	Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl is measured.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride	2 hours after the first oral administration of nefopam or Placebo.	Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride is measured.
Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde	2 hours after the first oral administration of nefopam or Placebo.	Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde is measured.
Persistent postoperative pain - DN4	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.

Trial Locations

Locations (1)

Département d'Anesthésie Réanimation, Groupement Hospitalier Nord, Hospices Civils de Lyon; 🇫🇷 Lyon, France