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Post-operative Analgesic Effect of Oral Nefopam (NefPO)

Primary Purpose

Postoperative Pain After a Total Knee Arthroplasty

Status

Recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Oral nefopam

Placebo

About this trial

This is an interventional treatment trial for Postoperative Pain After a Total Knee Arthroplasty focused on measuring Nefopam, Oral, postoperative pain, hyperalgesia, cerebrospinal fluid and plasma concentration, total knee arthroplasty

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

adult patients scheduled for a high tibial osteotomy 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NEFOPAM 60mg PO/ 8 hours

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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.

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.

Hyperalgesia - Allodynia zone

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

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)

Self reported safety outcomes

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

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.

Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam

Plasmatic and cerebrospinal fluid concentration of nefopam is measured.

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

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

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

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

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

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

Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride

Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride is measured.

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.

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.

Full Information

NCT ID

NCT04576078

First Posted

September 29, 2020

Last Updated

April 11, 2023

Sponsor

Hospices Civils de Lyon

1. Study Identification

Unique Protocol Identification Number

NCT04576078

Brief Title

Post-operative Analgesic Effect of Oral Nefopam

Acronym

NefPO

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 29, 2021 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

November 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Postoperative Pain After a Total Knee Arthroplasty

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Masking Description

Nefopam has a distinct bitter taste. A taste masking compound non interfering with chemical properties of the drug is used in both arms. Orally given mixture (nefopam or placebo) is prepared by an independent nurse in a separate location and given to a patient in patient's ward.

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

NEFOPAM 60mg PO/ 8 hours

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Oral nefopam

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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 Outcome Measure Information:

Title

Total morphine consumption within 24h after the surgery.

Description

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 Outcome Measure Information:

Title

Hyperalgesia - Pressure Pain Threshold

Description

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

Title

Hyperalgesia - Punctate Pain Intensity

Description

Time Frame

24 hours after the surgery

Title

Hyperalgesia - Allodynia zone

Description

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

Title

Pain intensity

Description

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

Title

Self reported safety outcomes

Description

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

Time Frame

24 hours after the surgery

Title

Measures Safety outcomes

Description

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

Title

Pharmacokinetics:Plasmatic and cerebrospinal fluid concentration of nefopam

Description

Plasmatic and cerebrospinal fluid concentration of nefopam is measured.

Time Frame