Pain, PostoperativePhase 3NCT00241332
Postoperative Pain After Orthopedic Surgery: Does it Help to Give Fentanyl Before Start of Remifentanil Based Anesthesia?
A Phase 3 study testing fentanyl in people with Pain, Postoperative, run by Ullevaal University Hospital at 1 site in Norway.
Trial summary
The aim of this trial is to examine the possibility that fentanyl 1,5 µgr/kg given intravenously (i.v.) before the start of remifentanil infusion for anesthesia gives less development of tolerance/hyperalgesia postoperative than fentanyl given at the end of surgery (the traditional method). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pain, Postoperative
- What is being tested?
- fentanyl
- How many people
- 100 participants
- Where
- 1 siteNorway
- Study dates
- Oct 2005to Jul 2006
- Phase
- Phase 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women and men > 18 years.
- Informed consent.
- Elective day-orthopedic surgery: damage to anterior cruciate ligament and/or posterior cruciate ligament with or without medial collateral ligament.
Who cannot join
- Patients who use nonsteroidal anti-inflammatory drugs (NSAID's) or are allergic to NSAID's.
- Patients using steroids, anti-emetics, drugs or opioids.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prophylaxis Against Postoperative Pain After Orthopedic Surgery: Does it Help to Give Fentanyl Before Start of Remifentanil/Propofol Based Anesthesia?
The aim of this trial is to examine the possibility that fentanyl 1,5 µgr/kg given intravenously (i.v.) before the start of remifentanil infusion for anesthesia gives less development of tolerance/hyperalgesia postoperative than fentanyl given at the end of surgery (the traditional method).
Read the detailed description
Postoperative pain can contribute to reduction in the patient's well-being and, if it is pronounced, delayed rehabilitation and an increase in the total cost for nursing and treatment.
Experimental studies has shown that infusion of remifentanil over some period of time, can result in acute opioid tolerance and hyperalgesia (1-2).
One clinical trial has shown that intraoperative infusion of remifentanil gives acute opioid tolerance with subsequent increased postoperative pain and increased opioid consume postoperative (3).
The development of opioid tolerance probably has several mechanisms. One topical mechanism is opioid induced influence of N-methyl-d-aspartate (NMDA)-receptor and its intracellular second-messenger-systems. This results in central sensitization to pain stimulus in the dorsal horn and the brain (4-5), with following development of hyperalgesia.
Several strategies can be successful to reduce or prevent opioid induced hyperalgesia, for example NMDA-receptor antagonists, alfa-2 agonists, opioid rotation or combination of opioids with different receptor selectivity (6-8).
The theoretical background for pre-treating the opioid receptor with an other opioid (fentanyl) that gives less tendency to hyperalgesia than remifentanil, is that it can reduce the development of tolerance and hyperalgesia of remifentanil.
The aim of this trial is to examine the possibility that i.v. administration of fentanyl 1,5 µgr/kg before start of remifentanil infusion for anesthesia gives less development of tolerance/hyperalgesia postoperative than fentanyl given in the end of surgery (the traditional method).
This is to be measured by less pain postoperative (VAS, visual analog scale, and a five point verbal rating scale) and less fentanyl consumed (measured by using PCA).
Literature:
- Vinik HR, Kissin I (1998) Rapid development of tolerance to analgesia during remifentanil infusion in human. Anesth Analg 86:1307-1311.
- Angst MS, Koppert W, Pahl I, Clark JD, Schmelz M (2003) Short-term infusion of the µ-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain 106:49-57.
- Guignard et al. (2000) Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 93:409-417.
- Larcher A, Laulin JP, Celerier E, Le Moal M, Simonnet G (1998) Acute tolerance associated with a single opioid administration: involvement of N-methyl-D-aspartate-dependent pain facilitatory systems. Neuroscience Vol 84:583-589.
- Celerier E, Laulin J, Larcher A, Le Moal M, Simonnet G (1999) Evidence for opiate-activated NMDA processes masking opiate analgesia in rats. Brain Research 849:18-25.
- Celerier E, Rivat C, Jun Y, Laulin JP, Larcher A, Reynier P, Simonnet G(2000) Long-lasting hyperalgesia induced by fentanyl in rats: preventive Effect of ketamin. Anesthesiology 92:465-472.
- Bie B, Fields HL, Williams JT, Pan ZZ (2003) Roles of a alfa-1 and alfa-2-adrenoreceptors in the nucleus raphe magnus in opioid analgesia and opioid abstinence-induced hyperalgesia. Journal of Neuroscience 23:7950-7957.
- Mao J, Prince DD, Caruso F, Mayer DJ (1996) Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats. Pain 67:361-368.
- Conditions
- Pain, Postoperative
- Being tested
- fentanyl
- Keywords
- pain, hyperalgesia, drug tolerance, remifentanil, fentanyl, Anterior Cruciate Ligament, Posterior Cruciate Ligament, Medial Collateral Ligament, Knee
- Medical subject headings
- Pain, Postoperative, Pain, Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fentanylDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Less use of postoperative opioids
Less visual analog scale (VAS) and verbal rating scale (VRS) in the treatment group
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2005 (estimated)
- Study startOct 2005
- Study completionJul 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 100 participants
Sponsor and investigators
- Lead sponsor
- Ullevaal University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oslo
- Investigators
- Johan Ræder, Prof.MD,Phd, Study director, Ullevaal University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00241332
- Sponsor's protocol ID
- 510-05165
- Status last verified
- Sep 2005
- First submitted
- 17 Oct 2005
- Last updated
- 6 Jul 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylaxis Against Postoperative Pain After Orthopedic Surgery: Does it Help to Give Fentanyl Before Start of Remifentanil/Propofol Based Anesthesia?
- ClinicalTrials.gov ID
- NCT00241332
- Acronym / sponsor ID
- 510-05165
- Conditions
- Pain, Postoperative
- Keywords
- pain, hyperalgesia, drug tolerance, remifentanil, fentanyl, Anterior Cruciate Ligament, Posterior Cruciate Ligament, Medial Collateral Ligament, Knee
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants
- Lead sponsor
- Ullevaal University HospitalUniversity, hospital or other
- Collaborators
- University of Oslo
- Study start
- Oct 2005
- Study completion
- Jul 2006 (actual)
- First posted
- 18 Oct 2005 (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 aim of this trial is to examine the possibility that fentanyl 1,5 µgr/kg given intravenously (i.v.) before the start of remifentanil infusion for anesthesia gives less development of tolerance/hyperalgesia postoperative than fentanyl given at the end of surgery (the traditional method).
Detailed description
Postoperative pain can contribute to reduction in the patient's well-being and, if it is pronounced, delayed rehabilitation and an increase in the total cost for nursing and treatment.
Experimental studies has shown that infusion of remifentanil over some period of time, can result in acute opioid tolerance and hyperalgesia (1-2).
One clinical trial has shown that intraoperative infusion of remifentanil gives acute opioid tolerance with subsequent increased postoperative pain and increased opioid consume postoperative (3).
The development of opioid tolerance probably has several mechanisms. One topical mechanism is opioid induced influence of N-methyl-d-aspartate (NMDA)-receptor and its intracellular second-messenger-systems. This results in central sensitization to pain stimulus in the dorsal horn and the brain (4-5), with following development of hyperalgesia.
Several strategies can be successful to reduce or prevent opioid induced hyperalgesia, for example NMDA-receptor antagonists, alfa-2 agonists, opioid rotation or combination of opioids with different receptor selectivity (6-8).
The theoretical background for pre-treating the opioid receptor with an other opioid (fentanyl) that gives less tendency to hyperalgesia than remifentanil, is that it can reduce the development of tolerance and hyperalgesia of remifentanil.
The aim of this trial is to examine the possibility that i.v. administration of fentanyl 1,5 µgr/kg before start of remifentanil infusion for anesthesia gives less development of tolerance/hyperalgesia postoperative than fentanyl given in the end of surgery (the traditional method).
This is to be measured by less pain postoperative (VAS, visual analog scale, and a five point verbal rating scale) and less fentanyl consumed (measured by using PCA).
Literature:
- Vinik HR, Kissin I (1998) Rapid development of tolerance to analgesia during remifentanil infusion in human. Anesth Analg 86:1307-1311.
- Angst MS, Koppert W, Pahl I, Clark JD, Schmelz M (2003) Short-term infusion of the µ-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain 106:49-57.
- Guignard et al. (2000) Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 93:409-417.
- Larcher A, Laulin JP, Celerier E, Le Moal M, Simonnet G (1998) Acute tolerance associated with a single opioid administration: involvement of N-methyl-D-aspartate-dependent pain facilitatory systems. Neuroscience Vol 84:583-589.
- Celerier E, Laulin J, Larcher A, Le Moal M, Simonnet G (1999) Evidence for opiate-activated NMDA processes masking opiate analgesia in rats. Brain Research 849:18-25.
- Celerier E, Rivat C, Jun Y, Laulin JP, Larcher A, Reynier P, Simonnet G(2000) Long-lasting hyperalgesia induced by fentanyl in rats: preventive Effect of ketamin. Anesthesiology 92:465-472.
- Bie B, Fields HL, Williams JT, Pan ZZ (2003) Roles of a alfa-1 and alfa-2-adrenoreceptors in the nucleus raphe magnus in opioid analgesia and opioid abstinence-induced hyperalgesia. Journal of Neuroscience 23:7950-7957.
- Mao J, Prince DD, Caruso F, Mayer DJ (1996) Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats. Pain 67:361-368.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Women and men > 18 years.
- Informed consent.
- Elective day-orthopedic surgery: damage to anterior cruciate ligament and/or posterior cruciate ligament with or without medial collateral ligament.
Key exclusion criteria (2 listed)
- Patients who use nonsteroidal anti-inflammatory drugs (NSAID's) or are allergic to NSAID's.
- Patients using steroids, anti-emetics, drugs or opioids.
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 |
|---|---|---|
| fentanyl | Drug | – |
Primary outcome
Less use of postoperative opioids
Less visual analog scale (VAS) and verbal rating scale (VRS) in the treatment group
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 6 Jul 2011.
Related trials for Pain, Postoperative
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
Recruiting
Effect of Cryotherapeutic and Nanotherapeutic Sodium Hypochlorite on Post-Operative Endodontic Pain.
Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
Active, not recruitingPhase 4
Effect of Dexmedetomidine on Postoperative Pain in Spinal Anesthesia for Cesarean Section at Assuit University Hospital
Cesarean Section
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.
Johan Ræder, Prof.MD,Phd study director
Ullevaal University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fentanyl in people with Pain, Postoperative, run by Ullevaal University Hospital at 1 site in Norway.
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 3 inclusion and 2 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 6 Jul 2011. 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 Norway. 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. 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 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?
Less use of postoperative opioids. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jul 2011.