Clinical trial NCT04576078: Post-operative Analgesic Effect of Oral Nefopam
Official title: Postoperative Analgesic Effect of Orally Administrated Nefopam After a Total Knee Arthroplasty: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Postoperative Pain After a Total Knee Arthroplasty
Keywords: Nefopam
Oral
postoperative pain
hyperalgesia
cerebrospinal fluid and plasma concentration
total knee arthroplasty
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2020-10-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Total morphine consumption within 24h after the surgery.
timeFrame: 24 hours after the surgery.
Secondary outcomes:
measure: Hyperalgesia - Pressure Pain Threshold
timeFrame: 24 hours after the surgery
measure: Hyperalgesia - Punctate Pain Intensity
timeFrame: 24 hours after the surgery
measure: Hyperalgesia - Allodynia zone
timeFrame: 24 hours after the surgery
measure: Pain intensity
timeFrame: 24 hours after the surgery and 3 months after the surgery
measure: Self reported safety outcomes
timeFrame: 24 hours after the surgery
measure: Measures Safety outcomes
timeFrame: 24 hours after the surgery
measure: Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam
timeFrame: 2 hours after the first oral administration of nefopam or Placebo.
measure: Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide
timeFrame: 2 hours after the first oral administration of nefopam or Placebo.
measure: Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde
timeFrame: 2 hours after the first oral administration of nefopam or Placebo.
measure: Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl
timeFrame: 2 hours after the first oral administration of nefopam or Placebo.
measure: Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride
timeFrame: 2 hours after the first oral administration of nefopam or Placebo.
measure: Persistent postoperative pain - DN4 (or DN2 by phone)
timeFrame: 3 months after the surgery
measure: Persistent postoperative pain - DN4
timeFrame: 4 months after the surgery
Other outcomes:
Locations:
city: Lyon
country: France
facility: Département d'Anesthésie Réanimation, Groupement Hospitalier Nord, Hospices Civils de Lyon
Study officials:
affiliation: Département d'Anesthésie Réanimation, Hopital de la Croix Rousse
name: Frederic AUBRUN, MD/PHD
role: PRINCIPAL_INVESTIGATOR
References: