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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Rennes University Hospital
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT01882530
First received: June 18, 2013
Last updated: August 8, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Post Operative Analgesia
Drug: Paracetamol
Drug: Nefopam
Drug: Ketoprofen
Drug: Morphine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA). [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Morphine consumption (mg) measured by patient controlled analgesia (PCA). [ Time Frame: Day 2, day 3 ] [ Designated as safety issue: No ]
  • Incidence of side effects associated with morphine: nausea, vomiting, sedation, urinary retention, pruritus. [ Time Frame: Day 3 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Incidence of chronic pain assessed by a telephone questionnaire 3 months after surgery (sub-study in 3 centers). [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  • Global satisfaction (measured after treatment) [ Time Frame: Day 3 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1000
Study Start Date: June 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01882530

Contacts
Contact: HELENE BELOEIL (0)2.99.28.42.00 ext +33 helene.beloeil@chu-rennes.fr

Locations
France
Karine Nouette-Gaulain Recruiting
Bordeaux, France
Contact: Karine Nouette-Gaulain         
Marcel Chauvin Recruiting
Boulogne, France
Contact: Marcel Chauvin         
Hawa Keita-Meyer Recruiting
Colombes, France
Contact: Hawa Keita-Meyer         
Dominique Fletcher Recruiting
Garches, France
Contact: Dominique Fletcher         
Pierre Albaladejo Recruiting
Grenoble, France
Contact: Pierre Albaladejo         
Frédéric Aubrun Recruiting
Lyon, France
Contact: Frédéric Aubrun         
Xavier Capdevila Recruiting
Montpellier, France
Contact: Xavier Capdevila         
Hervé Bouaziz Recruiting
Nancy, France
Contact: Hervé Bouaziz         
Karim Asehnoune Recruiting
Nantes, France
Contact: Karim Asehnoune         
Marc Raucoules Recruiting
Nice, France
Contact: Marc Raucoules         
Jacques Ripart Recruiting
Nîmes, France
Contact: Jacques Ripart         
Marc Beaussier Recruiting
Paris, France
Contact: Marc Beaussier         
Emmanuel Marret Recruiting
Paris, France
Contact: Emmanuel Marret         
Jean-Xavier Mazoit Recruiting
Paris, France
Contact: Jean-Xavier Mazoit         
Anissa Belbachir Recruiting
Paris, France
Contact: Anissa Belbachir         
Sébastien Bloc Recruiting
Quincy sous Sénart, France
Contact: Sébastien Bloc         
Jean-Marc Malinovsky Recruiting
Reims, France
Contact: Jean-Marc Malinovsky         
Marc Gentili Recruiting
St Grégoire, France
Contact: Marc Gentili         
Vincent Minville Recruiting
Toulouse, France
Contact: Vincent Minville         
Sponsors and Collaborators
Rennes University Hospital
Investigators
Study Chair: ERIC BELLISSANT Rennes University Hospital
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01882530     History of Changes
Other Study ID Numbers: 130505A-32
Study First Received: June 18, 2013
Last Updated: August 8, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

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

Additional relevant MeSH terms:
Acetaminophen
Nefopam
Ketoprofen
Analgesics, Non-Narcotic
Analgesics
Morphine
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics
Central Nervous System Depressants

ClinicalTrials.gov processed this record on August 21, 2014