Post Operative AnalgesiaPhase 4OCTOPUSNCT01882530
Non-opioid Analgesic Combination With Morphine for Postoperative Analgesia.
A Phase 4 study testing Paracetamol, Nefopam and Ketoprofen in people with Post Operative Analgesia, run by Rennes University Hospital at 19 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post Operative Analgesia
- What is being tested?
- Paracetamol, Nefopam and Ketoprofen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 223 participants
- Where
- 19 sitesFrance
- Study dates
- 23 Jul 2013to 16 Jan 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
France19 sites
Karine Nouette-Gaulain
Bordeaux
Marcel Chauvin
Boulogne
Hawa Keita-Meyer
Colombes
Dominique Fletcher
Garches
Pierre Albaladejo
Grenoble
Frédéric Aubrun
Lyon
Xavier Capdevila
Montpellier
Hervé Bouaziz
Nancy
Karim Asehnoune
Nantes
Marc Raucoules
Nice
Jacques Ripart
Nîmes
Anissa Belbachir
Paris
Emmanuel Marret
Paris
Jean-Xavier Mazoit
Paris
Marc Beaussier
Paris
Sébastien Bloc
Quincy-sous-Sénart
Jean-Marc Malinovsky
Reims
Marc Gentili
Saint-Grégoire
Vincent Minville
Toulouse
About this study
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.
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.
Read the 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
- Being tested
- Paracetamol, Nefopam, Ketoprofen, Morphine
- Keywords
- Post operative analgesia ;, Paracetamol ;, Ketoprofen ;, Nefopam ;, Morphine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParacetamolDrug
NefopamDrug
KetoprofenDrug
MorphineDrug
Also called All patients will receive morphine postoperatively (titration, then PCA).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Paracetamol; Drug: 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. Receives: Drug: Nefopam; Drug: 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. Receives: Drug: Ketoprofen; Drug: 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. Receives: Drug: Paracetamol; Drug: Nefopam; Drug: 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. Receives: Drug: Paracetamol; Drug: Ketoprofen; Drug: 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. Receives: Drug: Nefopam; Drug: Ketoprofen; Drug: 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. Receives: Drug: Paracetamol; Drug: Nefopam; Drug: Ketoprofen; Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA).
Measured: Day 1
Secondary outcomes (5)
Morphine consumption (mg) measured by patient controlled analgesia (PCA).
Measured: Day 2, day 3
Incidence of side effects associated with morphine: nausea, vomiting, sedation, urinary retention, pruritus.
Measured: Day 3
Area of hyperalgesia measured using a von Frey filament expressed in cm2, 48 hours after surgery (sub-study in 3 centers).
Measured: Day 2
Incidence of chronic pain assessed by a telephone questionnaire 3 months after surgery (sub-study in 3 centers).
Measured: Month 3
Global satisfaction (measured after treatment)
Measured: Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2013 (estimated)
- Study start23 Jul 2013
- Primary completion16 Jan 2016
- Study completion16 Jan 2016
Why it stopped: Practice on postoperative pain management changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post Operative AnalgesiaStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 223 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- ERIC BELLISSANT, Study chair, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01882530
- Sponsor's protocol ID
- 130505A-32
- Acronym
- OCTOPUS
- Status last verified
- Feb 2018
- First submitted
- 18 Jun 2013
- Last updated
- 6 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30915987
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01882530
- Acronym / sponsor ID
- OCTOPUS / 130505A-32
- Conditions
- Post Operative Analgesia
- Keywords
- Post operative analgesia ;, Paracetamol ;, Ketoprofen ;, Nefopam ;, Morphine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Practice on postoperative pain management changed
- Enrolment
- 223 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 23 Jul 2013 (actual)
- Primary completion
- 16 Jan 2016 (actual)
- Study completion
- 16 Jan 2016 (actual)
- First posted
- 20 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Control group C: Placebo | Placebo comparator | Drug: MorphineAll 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 P: Paracetamol | Experimental | Drug: Paracetamol, Drug: MorphineAll 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 N: Nefopam | Experimental | Drug: Nefopam, Drug: MorphineAll 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 K: Ketoprofen | Experimental | Drug: Ketoprofen, Drug: MorphineAll 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 PN: paracetamol and nefopam | Experimental | Drug: Paracetamol, Drug: Nefopam, Drug: MorphineAll 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 PK: paracetamol and ketoprofen | Experimental | Drug: Paracetamol, Drug: Ketoprofen, Drug: MorphineAll 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 NK: nefopam and ketoprofen | Experimental | Drug: Nefopam, Drug: Ketoprofen, Drug: MorphineAll 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 PNK: paracetamol, nefopam and ketoprofen | Experimental | Drug: Paracetamol, Drug: Nefopam, Drug: Ketoprofen, Drug: MorphineAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paracetamol | Drug | Group P: Paracetamol, Group PK: paracetamol and ketoprofen, Group PN: paracetamol and nefopam, Group PNK: paracetamol, nefopam and ketoprofen |
| Nefopam | Drug | Group N: Nefopam, Group NK: nefopam and ketoprofen, Group PN: paracetamol and nefopam, Group PNK: paracetamol, nefopam and ketoprofen |
| Ketoprofen | Drug | Group K: Ketoprofen, Group NK: nefopam and ketoprofen, Group PK: paracetamol and ketoprofen, Group PNK: paracetamol, nefopam and ketoprofen |
| MorphineAlso: All patients will receive morphine postoperatively (titration, then PCA). | Drug | Control group C: Placebo, Group K: Ketoprofen, Group N: Nefopam, Group NK: nefopam and ketoprofen, Group P: Paracetamol, Group PK: paracetamol and ketoprofen, Group PN: paracetamol and nefopam, Group PNK: paracetamol, nefopam and ketoprofen |
Primary outcome
Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA).
Time frame: Day 1
5 secondary outcomes
Morphine consumption (mg) measured by patient controlled analgesia (PCA).
Time frame: Day 2, day 3
Incidence of side effects associated with morphine: nausea, vomiting, sedation, urinary retention, pruritus.
Time frame: Day 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
Incidence of chronic pain assessed by a telephone questionnaire 3 months after surgery (sub-study in 3 centers).
Time frame: Month 3
Global satisfaction (measured after treatment)
Time frame: Day 3
Results and safety
The study was stopped early (reason given: Practice on postoperative pain management changed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2018.
- Derived from this study: PubMed 30915987Beloeil 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ERIC BELLISSANT study chair
Rennes University Hospital
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Paracetamol, Nefopam and Ketoprofen in people with Post Operative Analgesia, run by Rennes University Hospital at 19 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Practice on postoperative pain management changed). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA). (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01882530, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2018.