Non-opioid Analgesic Combination With Morphine for Postoperative Analgesia.

NCT ID: NCT01882530

Last Updated: 2018-02-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 223 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-23
• Study Completion Date: 2016-01-16

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.

Detailed Description

Since the description of the concept of balanced analgesia in the early 90's, the combination of different analgesic drugs and/or analgesia techniques is part of the standard management of postoperative analgesia. A recent survey conducted in France by Fletcher et al. showed that patients often received one or more NOA associated with an opioid. The benefit and risk of the use of opioids associated with NOA were recently reassessed as part of a formal recommendation of experts and detailed in a recent review. The analysis of the literature reveals a lack of comparison of the combinations of NOA with morphine for postoperative analgesia. For example, paracetamol and morphine in combination does not always allow a significant morphine-sparing effect compared with morphine alone and does not reduce the incidence of morphine side effects. A number of definitive answers has therefore yet to be found: Does NOA -morphine association allow an effective morphine-sparing effect? Is there an interest in prescribing several NOAs in association? If yes, what are the most interesting combinations in terms of morphine-sparing effect and safety?

Another question concerns the effects of NOA on postoperative hyperalgesia. This hyperalgesia, which results from surgery-related inflammation, is increased by consumption of morphine and not only contributes to the overall experience of postoperative pain but also to the chronicisation of postoperative pain. Since in clinical practice, hyperalgesia can be measured using specific tools (Von Frey filament type), our study will evaluate the anti-hyperalgesic effects of NOA on a subgroup of patients enrolled in the centers used to evaluate nociceptive thresholds.

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.

Conditions

Post Operative Analgesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Control group C: Placebo

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.

Group Type: PLACEBO_COMPARATOR

Morphine

Intervention Type: DRUG

Group P: Paracetamol

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.

Group Type: EXPERIMENTAL

Paracetamol

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Group N: Nefopam

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.

Group Type: EXPERIMENTAL

Nefopam

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Group K: Ketoprofen

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.

Group Type: EXPERIMENTAL

Ketoprofen

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Group PN: paracetamol and nefopam

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.

Group Type: EXPERIMENTAL

Paracetamol

Intervention Type: DRUG

Nefopam

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Group PK: paracetamol and ketoprofen

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.

Group Type: EXPERIMENTAL

Paracetamol

Intervention Type: DRUG

Ketoprofen

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Group NK: nefopam and ketoprofen

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.

Group Type: EXPERIMENTAL

Nefopam

Intervention Type: DRUG

Ketoprofen

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Group PNK: paracetamol, nefopam and ketoprofen

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.

Group Type: EXPERIMENTAL

Paracetamol

Intervention Type: DRUG

Nefopam

Intervention Type: DRUG

Ketoprofen

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Interventions

Paracetamol

Intervention Type: DRUG

Nefopam

Intervention Type: DRUG

Ketoprofen

Intervention Type: DRUG

Morphine

Intervention Type: DRUG

Other Intervention Names

All patients will receive morphine postoperatively (titration, then PCA).

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Disable adult person under guardianship
• Use of nitrous oxide during anesthesia protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ERIC BELLISSANT

Role: STUDY_CHAIR

Rennes University Hospital

Locations

Karine Nouette-Gaulain

Bordeaux, , France

Marcel Chauvin

Boulogne, , France

Hawa Keita-Meyer

Colombes, , France

Dominique Fletcher

Garches, , France

Pierre Albaladejo

Grenoble, , France

Frédéric Aubrun

Lyon, , France

Xavier Capdevila

Montpellier, , France

Hervé Bouaziz

Nancy, , France

Karim Asehnoune

Nantes, , France

Marc Raucoules

Nice, , France

Jacques Ripart

Nîmes, , France

Anissa Belbachir

Paris, , France

Emmanuel Marret

Paris, , France

Jean-Xavier Mazoit

Paris, , France

Marc Beaussier

Paris, , France

Sébastien Bloc

Quincy-sous-Sénart, , France

Jean-Marc Malinovsky

Reims, , France

Marc Gentili

Saint-Grégoire, , France

Vincent Minville

Toulouse, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 30915987 (View on PubMed)

Other Identifiers

130505A-32

Identifier Type: -

Identifier Source: org_study_id