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

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ClinicalTrials.gov Identifier: NCT01882530
Recruitment Status : Terminated (Practice on postoperative pain management changed)
First Posted : June 20, 2013
Last Update Posted : February 6, 2018
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

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 Type : Interventional  (Clinical Trial)
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 : July 23, 2013
Actual Primary Completion Date : January 16, 2016
Actual Study Completion Date : January 16, 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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



Primary Outcome Measures :
  1. Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA). [ Time Frame: Day 1 ]

Secondary Outcome Measures :
  1. Morphine consumption (mg) measured by patient controlled analgesia (PCA). [ Time Frame: Day 2, day 3 ]
  2. Incidence of side effects associated with morphine: nausea, vomiting, sedation, urinary retention, pruritus. [ Time Frame: Day 3 ]
  3. Area of hyperalgesia measured using a von Frey filament expressed in cm2, 48 hours after surgery (sub-study in 3 centers). [ Time Frame: Day 2 ]
  4. Incidence of chronic pain assessed by a telephone questionnaire 3 months after surgery (sub-study in 3 centers). [ Time Frame: Month 3 ]
  5. Global satisfaction (measured after treatment) [ Time Frame: Day 3 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01882530


Locations
France
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
St Grégoire, France
Vincent Minville
Toulouse, France
Sponsors and Collaborators
Rennes University Hospital
Investigators
Study Chair: ERIC BELLISSANT Rennes University Hospital

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01882530     History of Changes
Other Study ID Numbers: 130505A-32
First Posted: June 20, 2013    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: February 2018

Keywords provided by Rennes University Hospital:
Post operative analgesia ;
Paracetamol ;
Ketoprofen ;
Nefopam ;
Morphine

Additional relevant MeSH terms:
Agnosia
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Morphine
Analgesics
Acetaminophen
Ketoprofen
Nefopam
Analgesics, Non-Narcotic
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action