HyperalgesiaPhase 2/3NefalCardNCT00413257
Effects of Nefopam on Hyperalgesia After Cardiac Surgery
A Phase 2/3 study testing Nefopam and néfopam in people with Hyperalgesia and Pain, Postoperative, run by University Hospital, Bordeaux at 1 site in France.
Trial summary
Postoperative pain after major surgery is consecutive not only to the nociceptive inputs coming from the surgical lesion, but also to peripheral and central neuronal sensitization. This lead to postoperative hyperalgesia and allodynia that are enhanced by the per operative use of high opioid doses. Read more about this study
- Who is it for?
- Ages 55 to 75 years
- Conditions the study is for
- Hyperalgesia, Pain, Postoperative, Pain, Chronic Disease
- What is being tested?
- Nefopam and néfopam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2006to Nov 2008
- Phase
- Phase 2/3
- 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 55 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 55-75 years old
- ASA score: 1-3
- Patients scheduled for Cardiac surgery with median sternotomy for : single valve replacement or Bentall or Benson or Tyron David surgery, single or multiple Cardiac Artery Bypass Grafting (CABG) , combined surgery (valve replacement + CABG) without preoperative risk of postoperative complications
- Informed consent obtained from the patient
Who cannot join
- Drug or alcohol abuse history
- Analgesic or opioid consumption within the 12hs preceding the surgery
- Chronic use of analgesic drugs or history of chronic pain
- Convulsion or epilepsy history
- Glaucoma history
- Disability to understand morphine PCA use
- Allergy to nefopam
Trial locations and contacts
1 site in 1 country.
France1 site
Département d'Anesthésie-Réanimation II - Hôpital cardiologique - Groupe Hospitalier Sud, CHU de Bordeaux - 4, Av de Magellan
Pessac, 33604
About this study
Official title: Study of the Effects of Nefopam on Hyperalgesia Following Sternotomy in Cardiac Surgery
Postoperative pain after major surgery is consecutive not only to the nociceptive inputs coming from the surgical lesion, but also to peripheral and central neuronal sensitization. This lead to postoperative hyperalgesia and allodynia that are enhanced by the per operative use of high opioid doses. Anti-NMDA drugs have been reported as able to reduce this sensitization process and then to decrease acute morphine tolerance during the postoperative period. Nefopam has been lately shown to combine in experimental trials analgesic and anti hyperalgesic effects. The aim of this study is to compare anti-hyperalgesic effects of nefopam given either before incision and continuously for the following 48hours or starting from the end of the surgery and given for 48hours to a control group that would receive placebo for 48hours. Postoperative analgesia will be based on morphine PCA. Pain scores, hyperalgesia, allodynia, postoperative morphine consumption, and development of chronic pain will be the main criteria that will be evaluated during this study
Read the detailed description
Introduction :
Postoperative pain is not only a consequence of the surgical lesion, but is also related to sensitization processes that appear in peripheral and central nerves. This sensitization induce clinically hyperalgesia and allodynia. From an experimental viewpoint it comes mainly from a central activation of NMDA receptors in neurons that conduct the nociceptive message.
Recent studies have shown that high-dose opioids were able, via NMDA receptors, to enhance postoperative hyperalgesia and to increase pain scores and morphine consumption after surgery. Nevertheless per operative use of opioid is still necessary to avoid per operative stress and systemic consequence of the surgical stimulation.
Some drugs (ketamine, nitrous oxide…) succeeded in reducing postoperative hyperalgesia and pains scores and acute morphine tolerance. They also were able to decrease pain chronicization.
Nefopam, well known as an analgesic since the 80's, presents both analgesic and anti hyperalgesic properties as lately demonstrated in experimental trials. Nevertheless these anti hyperalgesic properties have never been evaluated in humans scheduled for cardiac surgery. Nefopam administration could reduce acute morphine tolerance and could enhance postoperative pain management by reducing sensitization processes and hyperalgesia.
Objective :
The main purpose of this clinical trial will be to evaluate in patients scheduled for cardiac surgery with sternotomy the nefopam effects on the nociceptive threshold evaluated with dynamic Von Frey mechanical stimulation.
The secondary objectives will evaluate static hyperalgesia, postoperative pain scores, morphine consumption, cognitive functions, and development of chronic pain and dysesthesia.
Methods :
Prospective, randomized, double-blind study that will compare three parallel groups that will receive the same per operative anesthesia except for the nefopam doses.
Group 1: nefopam infusion will start before the surgical incision, at the induction time of anesthesia and will be continued until postoperative H48. Group 2: nefopam administration will start at the end of the surgery and will be continued until postoperative H48. Group 3: control group that will receive a placebo from the induction time of anesthesia until H48. All patients will receive postoperatively morphine infusion following the Patient Controlled Analgesia concept.
Number of patients to be included : 90 Duration of the study : 2 years Start : second semester of 2006
Expected result :
Reduction of the extend of hyperalgesia around the wound evaluated with dynamic Von Frey mechanical stimulation more than 20%.
- Conditions
- Hyperalgesia, Pain, Postoperative, Pain, Chronic Disease
- Being tested
- Nefopam, néfopam, Placebo comparator
- Keywords
- Postoperative Hyperalgesia, cardiac Surgical Procedures, Nefopam, Randomized Controlled Trials, Pain and chronic disease
- Medical subject headings
- Hyperalgesia, Pain, Postoperative, Pain, Chronic Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NefopamDrug
0,3mg/kg IV bolus preoperative and 65 µg/kg/h during H48 postoperative
néfopamDrug
bolus Néfopam (0,3mg/kg) during 10 min at the end of surgery and 65 µg/kg/h during postoperative H48
Placebo comparatorDrug
bolus NaCl during 10 min at the end of surgery and during postoperative H48
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | nefopam infusion will start before the surgical incision, at the induction time of anesthesia and will be continued until postoperative H48 Receives: Drug: Nefopam |
| 2 | Experimental | nefopam administration will start at the end of the surgery and will be continued until postoperative H48 Receives: Drug: néfopam |
| 3 | Placebo comparator | control group that will receive a placebo from the induction time of anesthesia until H48 Receives: Drug: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nociceptive threshold evaluated with Von Frey mechanical dynamic stimulation. This will start 10cm far from the wound on a perpendicular line to the wound and will be conducted by 1cm step to the wound until the patient explains the stimulation
Measured: H 24
Secondary outcomes (4)
static hyperalgesia with Von Frey stimulation 1cm far from the middle of the wound, on the right side of the wound.
Measured: 1, 2, 4 and 7 days after intervention
Morphine consumption
Measured: over the 48 H postoperative
Pain scores evaluation
Measured: Acute pain (1, 2, 4 and 7 days after intervention) / Chronic Pain (3, 6 and 12 month)
Cognitive functions evaluation
Measured: 1, 2, 4 and 7 days after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionDec 2007
- Study completionNov 2008
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 HyperalgesiaStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Investigators
- Philippe RICHEBE, Dr, Principal investigator, University Hospital, BordeauxAntoine BENARD, Dr, Study chair, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00413257
- Sponsor's protocol ID
- 7813
- Other IDs
- 2005-033
- Acronym
- NefalCard
- Status last verified
- May 2010
- First submitted
- 18 Dec 2006
- Last updated
- 28 May 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Richebe P, Picard W, Rivat C, Jelacic S, Branchard O, Leproust S, Cahana A, Janvier G. Effects of nefopam on early postoperative hyperalgesia after cardiac surgery. J Cardiothorac Vasc Anesth. 2013 Jun;27(3):427-35. doi: 10.1053/j.jvca.2012.08.015. Epub 2012 Oct 12.
PubMed 23063945
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effects of Nefopam on Hyperalgesia Following Sternotomy in Cardiac Surgery
- ClinicalTrials.gov ID
- NCT00413257
- Acronym / sponsor ID
- NefalCard / 7813
- Conditions
- Hyperalgesia, Pain, Postoperative, Pain, Chronic Disease
- Keywords
- Postoperative Hyperalgesia, cardiac Surgical Procedures, Nefopam, Randomized Controlled Trials, Pain and chronic disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- Dec 2006
- Primary completion
- Dec 2007 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 19 Dec 2006 (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.
Postoperative pain after major surgery is consecutive not only to the nociceptive inputs coming from the surgical lesion, but also to peripheral and central neuronal sensitization. This lead to postoperative hyperalgesia and allodynia that are enhanced by the per operative use of high opioid doses. Anti-NMDA drugs have been reported as able to reduce this sensitization process and then to decrease acute morphine tolerance during the postoperative period. Nefopam has been lately shown to combine in experimental trials analgesic and anti hyperalgesic effects. The aim of this study is to compare anti-hyperalgesic effects of nefopam given either before incision and continuously for the following 48hours or starting from the end of the surgery and given for 48hours to a control group that would receive placebo for 48hours. Postoperative analgesia will be based on morphine PCA. Pain scores, hyperalgesia, allodynia, postoperative morphine consumption, and development of chronic pain will be the main criteria that will be evaluated during this study
Detailed description
Introduction :
Postoperative pain is not only a consequence of the surgical lesion, but is also related to sensitization processes that appear in peripheral and central nerves. This sensitization induce clinically hyperalgesia and allodynia. From an experimental viewpoint it comes mainly from a central activation of NMDA receptors in neurons that conduct the nociceptive message.
Recent studies have shown that high-dose opioids were able, via NMDA receptors, to enhance postoperative hyperalgesia and to increase pain scores and morphine consumption after surgery. Nevertheless per operative use of opioid is still necessary to avoid per operative stress and systemic consequence of the surgical stimulation.
Some drugs (ketamine, nitrous oxide…) succeeded in reducing postoperative hyperalgesia and pains scores and acute morphine tolerance. They also were able to decrease pain chronicization.
Nefopam, well known as an analgesic since the 80's, presents both analgesic and anti hyperalgesic properties as lately demonstrated in experimental trials. Nevertheless these anti hyperalgesic properties have never been evaluated in humans scheduled for cardiac surgery. Nefopam administration could reduce acute morphine tolerance and could enhance postoperative pain management by reducing sensitization processes and hyperalgesia.
Objective :
The main purpose of this clinical trial will be to evaluate in patients scheduled for cardiac surgery with sternotomy the nefopam effects on the nociceptive threshold evaluated with dynamic Von Frey mechanical stimulation.
The secondary objectives will evaluate static hyperalgesia, postoperative pain scores, morphine consumption, cognitive functions, and development of chronic pain and dysesthesia.
Methods :
Prospective, randomized, double-blind study that will compare three parallel groups that will receive the same per operative anesthesia except for the nefopam doses.
Group 1: nefopam infusion will start before the surgical incision, at the induction time of anesthesia and will be continued until postoperative H48. Group 2: nefopam administration will start at the end of the surgery and will be continued until postoperative H48. Group 3: control group that will receive a placebo from the induction time of anesthesia until H48. All patients will receive postoperatively morphine infusion following the Patient Controlled Analgesia concept.
Number of patients to be included : 90 Duration of the study : 2 years Start : second semester of 2006
Expected result :
Reduction of the extend of hyperalgesia around the wound evaluated with dynamic Von Frey mechanical stimulation more than 20%.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Nefopamnefopam infusion will start before the surgical incision, at the induction time of anesthesia and will be continued until postoperative H48 |
| 2 | Experimental | Drug: néfopamnefopam administration will start at the end of the surgery and will be continued until postoperative H48 |
| 3 | Placebo comparator | Drug: Placebo comparatorcontrol group that will receive a placebo from the induction time of anesthesia until H48 |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 55-75 years old
- ASA score: 1-3
- Patients scheduled for Cardiac surgery with median sternotomy for : single valve replacement or Bentall or Benson or Tyron David surgery, single or multiple Cardiac Artery Bypass Grafting (CABG) , combined surgery (valve replacement + CABG) without preoperative risk of postoperative complications
- Informed consent obtained from the patient
Key exclusion criteria (7 listed)
- Drug or alcohol abuse history
- Analgesic or opioid consumption within the 12hs preceding the surgery
- Chronic use of analgesic drugs or history of chronic pain
- Convulsion or epilepsy history
- Glaucoma history
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 |
|---|---|---|
| Nefopam0,3mg/kg IV bolus preoperative and 65 µg/kg/h during H48 postoperative | Drug | 1 |
| néfopambolus Néfopam (0,3mg/kg) during 10 min at the end of surgery and 65 µg/kg/h during postoperative H48 | Drug | 2 |
| Placebo comparatorbolus NaCl during 10 min at the end of surgery and during postoperative H48 | Drug | 3 |
Primary outcome
Nociceptive threshold evaluated with Von Frey mechanical dynamic stimulation. This will start 10cm far from the wound on a perpendicular line to the wound and will be conducted by 1cm step to the wound until the patient explains the stimulation
Time frame: H 24
4 secondary outcomes
static hyperalgesia with Von Frey stimulation 1cm far from the middle of the wound, on the right side of the wound.
Time frame: 1, 2, 4 and 7 days after intervention
Morphine consumption
Time frame: over the 48 H postoperative
Pain scores evaluation
Time frame: Acute pain (1, 2, 4 and 7 days after intervention) / Chronic Pain (3, 6 and 12 month)
Cognitive functions evaluation
Time frame: 1, 2, 4 and 7 days after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2010.
- Derived from this study: PubMed 23063945Richebe P, Picard W, Rivat C, Jelacic S, Branchard O, Leproust S, Cahana A, Janvier G. Effects of nefopam on early postoperative hyperalgesia after cardiac surgery. J Cardiothorac Vasc Anesth. 2013 Jun;27(3):427-35. doi: 10.1053/j.jvca.2012.08.015. Epub 2012 Oct 12.
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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.
Philippe RICHEBE, Dr principal investigator
University Hospital, Bordeaux
Antoine BENARD, Dr study chair
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Nefopam and néfopam in people with Hyperalgesia and Pain, Postoperative, run by University Hospital, Bordeaux at 1 site 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 4 inclusion and 7 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: finished, as of the sponsor's last update on 28 May 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Nociceptive threshold evaluated with Von Frey mechanical dynamic stimulation. This will start 10cm far from the wound on a perpendicular line to the wound and will be conducted by 1cm step to the wound until the patient explains the stimulation (time frame: H 24). 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 NCT00413257, 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 28 May 2010.