OCTOPUS: Non-opioid Analgesic Combination With Morphine for Postoperative Analgesia.

Sponsor

Rennes University Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT01882530

Collaborator

(none)

223

Enrollment

Locations

Arms

29.8

Actual Duration (Months)

11.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Post Operative Analgesia	Drug: Paracetamol Drug: Nefopam Drug: Ketoprofen Drug: Morphine	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

223 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Prospective, Controlled Versus Placebo, Randomized, Double-blind Study, Evaluating the Value of Non-opioid Analgesic Combination (Based on Paracetamol, Nefopam, Ketoprofen) for Postoperative Analgesia.

Actual Study Start Date :

Jul 23, 2013

Actual Primary Completion Date :

Jan 16, 2016

Actual Study Completion Date :

Jan 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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.	Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).
Experimental: 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.	Drug: Paracetamol Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).
Experimental: 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.	Drug: Nefopam Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).
Experimental: 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.	Drug: Ketoprofen Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).
Experimental: 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.	Drug: Paracetamol Drug: Nefopam Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).
Experimental: 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.	Drug: Paracetamol Drug: Ketoprofen Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).
Experimental: 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.	Drug: Nefopam Drug: Ketoprofen Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).
Experimental: 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.	Drug: Paracetamol Drug: Nefopam Drug: Ketoprofen Drug: Morphine Other Names: All patients will receive morphine postoperatively (titration, then PCA).

Outcome Measures

Primary Outcome Measures

Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA). [Day 1]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Karine Nouette-Gaulain	Bordeaux	France
2	Marcel Chauvin	Boulogne	France
3	Hawa Keita-Meyer	Colombes	France
4	Dominique Fletcher	Garches	France
5	Pierre Albaladejo	Grenoble	France
6	Frédéric Aubrun	Lyon	France
7	Xavier Capdevila	Montpellier	France
8	Hervé Bouaziz	Nancy	France
9	Karim Asehnoune	Nantes	France
10	Marc Raucoules	Nice	France
11	Jacques Ripart	Nîmes	France
12	Anissa Belbachir	Paris	France
13	Emmanuel Marret	Paris	France
14	Jean-Xavier Mazoit	Paris	France
15	Marc Beaussier	Paris	France
16	Sébastien Bloc	Quincy sous Sénart	France
17	Jean-Marc Malinovsky	Reims	France
18	Marc Gentili	St Grégoire	France
19	Vincent Minville	Toulouse	France