Effects of Nefopam on Hyperalgesia After Cardiac Surgery (NefalCard)

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00413257
First received: December 18, 2006
Last updated: May 27, 2010
Last verified: May 2010
  Purpose

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


Condition Intervention Phase
Hyperalgesia
Pain, Postoperative
Pain, Chronic Disease
Drug: Nefopam
Drug: néfopam
Drug: Placebo comparator
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of the Effects of Nefopam on Hyperalgesia Following Sternotomy in Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Morphine consumption [ Time Frame: over the 48 H postoperative ] [ Designated as safety issue: No ]
  • Pain scores evaluation [ Time Frame: Acute pain (1, 2, 4 and 7 days after intervention) / Chronic Pain (3, 6 and 12 month) ] [ Designated as safety issue: No ]
  • Cognitive functions evaluation [ Time Frame: 1, 2, 4 and 7 days after intervention ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: December 2006
Study Completion Date: November 2008
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
nefopam infusion will start before the surgical incision, at the induction time of anesthesia and will be continued until postoperative H48
Drug: Nefopam
0,3mg/kg IV bolus preoperative and 65 µg/kg/h during H48 postoperative
Experimental: 2
nefopam administration will start at the end of the surgery and will be continued until postoperative H48
Drug: néfopam
bolus Néfopam (0,3mg/kg) during 10 min at the end of surgery and 65 µg/kg/h during postoperative H48
Placebo Comparator: 3
control group that will receive a placebo from the induction time of anesthesia until H48
Drug: Placebo comparator
bolus NaCl during 10 min at the end of surgery and during postoperative H48

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%.

  Eligibility

Ages Eligible for Study:   55 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00413257

Locations
France
Département d'Anesthésie-Réanimation II - Hôpital cardiologique - Groupe Hospitalier Sud, CHU de Bordeaux - 4, Av de Magellan
Pessac, France, 33604
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: Philippe RICHEBE, Dr University Hospital, Bordeaux
Study Chair: Antoine BENARD, Dr University Hospital, Bordeaux
  More Information

No publications provided by University Hospital, Bordeaux

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jean-Pierre LEROY / Clinical Research and Innovation Director, University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00413257     History of Changes
Other Study ID Numbers: 7813, 2005-033
Study First Received: December 18, 2006
Last Updated: May 27, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Postoperative Hyperalgesia
cardiac Surgical Procedures
Nefopam
Randomized Controlled Trials
Pain and chronic disease

Additional relevant MeSH terms:
Chronic Disease
Hyperalgesia
Pain, Postoperative
Chronic Pain
Disease Attributes
Pathologic Processes
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Postoperative Complications
Pain
Nefopam
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 11, 2014