Postoperative analgesic effect of orally administrated nefopam after a total knee arthroplasty: a randomized controlled trial (NefPO)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04]

Trial duration

29 Jun 2021 → ongoing

Decision date (initial)

2024-07-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

APICIL

External identifiers

EU CT number

2024-513796-40-00

EudraCT number

2020-002955-40

ClinicalTrials.gov

NCT04576078

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this study is to measure whether orally administered nefopam significantly reduces morphine consumption at 24h after total knee replacement (TKR) surgery in adults compared with placebo.

Secondary objectives 8

1. To compare the efficacy of nefopam PO with placebo in reducing the prevalence of persistent postoperative pain with a neuropathic component.
2. To compare the efficacy of nefopam PO versus placebo in reducing perioperative primary (at the surgical site) and secondary (at a distance) hyperalgesia.
3. To compare the efficacy of nefopam PO versus placebo in reducing allodynia.
4. To compare the efficacy of nefopam PO versus placebo in reducing acute postoperative pain.
5. To assess the tolerability of nefopam PO.
6. To investigate and quantify the intrathecal distribution of nefopam and its main metabolites (nefopam-beta-D-glucuronide, nefopam-N-oxide, nefopam-N-demethyl, nefopam hydrochoride).
7. To measure plasma and CSF nefopam concentration 2h00 after oral nefopam or placebo.
8. To measure plasma and CSF concentrations of the above-mentioned nefopam metabolites 2h00 after oral administration of nefopam or placebo.

Conditions and MedDRA coding

Postoperative pain after a total knee arthroplasty

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patient over 18.
2. Patient scheduled for primary PTG under spinal anesthesia, in the orthopedics department of the Croix-Rousse hospital.
3. Patient with an American Society of Anesthesiology (ASA) score between I and III.
4. Patient having agreed to take part in the study and having signed the informed consent form.
5. Patient entitled to social security benefits.
6. Patient willing to return for all study visits.

Exclusion criteria 7

1. 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)
2. 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)
3. Current treatment with benzodiazepines, anxiolytics, antidepressants, histamine H1 antagonists, neuroleptics, baclofen, thalidomide, barbiturates
4. Medical history of gastric or esophageal surgery.
5. Phenylketonuria
6. Pregnancy or breastfeeding
7. Past use of oral nefopam

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 13

1. Pressure Pain Threshold
2. Punctate Pain Intensity
3. Allodynia zone
4. Pain intensity
5. Self reported safety outcomes
6. Measures of safety outcomes
7. Plasmatic and cerebrospinal fluid concentration of nefopam
8. Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide
9. Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde
10. Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl
11. Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride
12. Persistent postoperative pain - DN4 (or DN2 by phone)
13. Persistent postoperative pain - DN4

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr AUBRUN

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr AUBRUN

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications