NCT01882530

Brief Summary

The combination of different analgesic drugs and/or analgesia techniques is part of the standard management of postoperative analgesia. The analysis of the literature reveals a lack of comparison of the associations of non-opioid analgesic (NOA) with morphine for postoperative analgesia. The objectives of this study are :

  • comparing the morphine sparing effect of different combination of 3 NOA (paracetamol, nefopam, ketoprofen) for postoperative analgesia.
  • determining whether the morphine-sparing effect is associated with or without a reduction in the incidence of morphine side effects.
  • evaluating the effects of NOA on postoperative hyperalgesia.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
223

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jul 2013

Typical duration for phase_4

Geographic Reach
1 country

19 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 18, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 20, 2013

Completed
1 month until next milestone

Study Start

First participant enrolled

July 23, 2013

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 16, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 16, 2016

Completed
Last Updated

February 6, 2018

Status Verified

February 1, 2018

Enrollment Period

2.5 years

First QC Date

June 18, 2013

Last Update Submit

February 2, 2018

Conditions

Post Operative Analgesia

Keywords

Post operative analgesia ;Paracetamol ;Ketoprofen ;Nefopam ;Morphine

Outcome Measures

Primary Outcomes (1)

  • Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA).

    Day 1

Secondary Outcomes (5)

  • Morphine consumption (mg) measured by patient controlled analgesia (PCA).

    Day 2, day 3

  • Incidence of side effects associated with morphine: nausea, vomiting, sedation, urinary retention, pruritus.

    Day 3

  • Area of hyperalgesia measured using a von Frey filament expressed in cm2, 48 hours after surgery (sub-study in 3 centers).

    Day 2

  • Incidence of chronic pain assessed by a telephone questionnaire 3 months after surgery (sub-study in 3 centers).

    Month 3

  • Global satisfaction (measured after treatment)

    Day 3

Study Arms (8)

Control group C: Placebo

PLACEBO COMPARATOR

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: Morphine

Group P: Paracetamol

EXPERIMENTAL

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: ParacetamolDrug: Morphine

Group N: Nefopam

EXPERIMENTAL

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: NefopamDrug: Morphine

Group K: Ketoprofen

EXPERIMENTAL

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: KetoprofenDrug: Morphine

Group PN: paracetamol and nefopam

EXPERIMENTAL

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: ParacetamolDrug: NefopamDrug: Morphine

Group PK: paracetamol and ketoprofen

EXPERIMENTAL

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: ParacetamolDrug: KetoprofenDrug: Morphine

Group NK: nefopam and ketoprofen

EXPERIMENTAL

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: NefopamDrug: KetoprofenDrug: Morphine

Group PNK: paracetamol, nefopam and ketoprofen

EXPERIMENTAL

All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.

Drug: ParacetamolDrug: NefopamDrug: KetoprofenDrug: Morphine

Interventions

ParacetamolDRUG
Group P: ParacetamolGroup PK: paracetamol and ketoprofenGroup PN: paracetamol and nefopamGroup PNK: paracetamol, nefopam and ketoprofen
NefopamDRUG
Group N: NefopamGroup NK: nefopam and ketoprofenGroup PN: paracetamol and nefopamGroup PNK: paracetamol, nefopam and ketoprofen
KetoprofenDRUG
Group K: KetoprofenGroup NK: nefopam and ketoprofenGroup PK: paracetamol and ketoprofenGroup PNK: paracetamol, nefopam and ketoprofen
MorphineDRUG
Also known as: All patients will receive morphine postoperatively (titration, then PCA).
Control group C: PlaceboGroup K: KetoprofenGroup N: NefopamGroup NK: nefopam and ketoprofenGroup P: ParacetamolGroup PK: paracetamol and ketoprofenGroup PN: paracetamol and nefopamGroup PNK: paracetamol, nefopam and ketoprofen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adults older than 18 years
  • Receiving scheduled surgery requiring the use of a PCA to treat postoperative pain
  • Patients with a written informed consent
  • Patients with a written informed consent for the sub-study on hyperalgesia (patients in the centers concerned)
  • Affiliate to a social security system

You may not qualify if:

  • Allergy to morphine, paracetamol, nefopam or ketoprofen or to any of their excipients
  • Absorption of morphine and / or NOA within 24 hours before surgery
  • Absorption of methadone within 48 hours before surgery
  • History of epilepsy
  • Renal insufficiency (creatinin clearance \<30 ml / min MDRD)
  • Hepatic insufficiency
  • Severe respiratory insufficiency
  • Pregnancy or breastfeeding women
  • History of seizures
  • Symptomatic urethroprostatic disorders
  • Angle-closure glaucoma
  • Gastrointestinal, cerebrovascular or other evolving bleedings
  • Active peptic ulcer or active gastritis
  • Severe heart failure
  • History of asthma triggered by taking ketoprofen or similar substances
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Karine Nouette-Gaulain

Bordeaux, France

Location

Marcel Chauvin

Boulogne, France

Location

Hawa Keita-Meyer

Colombes, France

Location

Dominique Fletcher

Garches, France

Location

Pierre Albaladejo

Grenoble, France

Location

Frédéric Aubrun

Lyon, France

Location

Xavier Capdevila

Montpellier, France

Location

Hervé Bouaziz

Nancy, France

Location

Karim Asehnoune

Nantes, France

Location

Marc Raucoules

Nice, France

Location

Jacques Ripart

Nîmes, France

Location

Anissa Belbachir

Paris, France

Location

Emmanuel Marret

Paris, France

Location

Jean-Xavier Mazoit

Paris, France

Location

Marc Beaussier

Paris, France

Location

Sébastien Bloc

Quincy-sous-Sénart, France

Location

Jean-Marc Malinovsky

Reims, France

Location

Marc Gentili

Saint-Grégoire, France

Location

Vincent Minville

Toulouse, France

Location

Related Publications (1)

  • Beloeil H, Albaladejo P, Sion A, Durand M, Martinez V, Lasocki S, Futier E, Verzili D, Minville V, Fessenmeyer C, Belbachir A, Aubrun F, Renault A, Bellissant E; OCTOPUS group. Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study. Br J Anaesth. 2019 Jun;122(6):e98-e106. doi: 10.1016/j.bja.2018.10.058. Epub 2018 Dec 29.

    PMID: 30915987DERIVED

MeSH Terms

Interventions

AcetaminophenNefopamKetoprofenMorphine

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAminesOxazocinesAzocinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPhenylpropionatesAcids, CarbocyclicCarboxylic AcidsMorphine DerivativesMorphinansOpiate AlkaloidsAlkaloidsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic Compounds

Study Officials

  • ERIC BELLISSANT

    Rennes University Hospital

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 18, 2013

First Posted

June 20, 2013

Study Start

July 23, 2013

Primary Completion

January 16, 2016

Study Completion

January 16, 2016

Last Updated

February 6, 2018

Record last verified: 2018-02

Locations

FR(19)