Hyperalgesia, SecondaryPhase 4NCT00785863
Modulation of Remifentanil-induced Postinfusion Hyperalgesia
A Phase 4 study testing Remifentanil, Ketorolac and remifentanil and Parecoxib and remifentanil in people with Hyperalgesia, Secondary, run by Ullevaal University Hospital at 1 site in Norway.
Trial summary
In addition to alleviate pain there is growing evidence that µ-opioids enhance pain. This problem is known as opioid induced hyperalgesia(OIH).The NMDA receptor is involved in opioid induced hyperalgesia it may be possible to block OIH by cyclooxygenase inhibitors. Read more about this study
- Who is it for?
- Ages 18 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hyperalgesia, Secondary
- What is being tested?
- Remifentanil, Ketorolac and remifentanil and Parecoxib and remifentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteNorway
- Study dates
- Dec 2008to Apr 2009
- 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 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers
Who cannot join
- Allergy to the drugs used in the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans
In addition to alleviate pain there is growing evidence that µ-opioids enhance pain. This problem is known as opioid induced hyperalgesia(OIH).The NMDA receptor is involved in opioid induced hyperalgesia it may be possible to block OIH by cyclooxygenase inhibitors. This has been demonstrated with parecoxib, a COX-II inhibitor, in a experimental pain model.Both COX-1 and COX-2 are expressed in the spinal cord. It would be of interest to investigate whether a COX-1 preferring inhibitor like ketorolac also can reduce opioid induced hyperalgesic in this experimental pain model.
Read the detailed description
Remifentanil is an fast acting opioid which has become very popular to use during surgery.
There are studies, both experimental 1-3 and clinical 4;5, which indicate that remifentanil after end of infusion trigger enhanced pain experience and enhanced opioid consumption postoperatively.
Therefore it is important to look at possibilities to block this enhanced pain experience (opioid induced hyperalgesia - OIH). Ketamin has demonstrated to block this effect 5;6 through the NMDA receptor. Unfortunately ketamin has some seriously side-effects like hallucinations, and is therefore not suitable in ordenary clinical use.
Recently, it has been demonstrated that parecoxib (a COX-2 inhibitor) can prevent remifentanil-induced postinfusion hyperalgesia in a study on healthy volunteers.7 COX-2 inhibitors have some disadvantages because of the longterm adverse effects like cardiac arrest. Therefore it would be of interest to look at a COX-1 preferring NSAID, like ketorolac, to see if also non-selective NSAIDs can partly block remifentanil-induced postinfusion hyperalgesia.
To investigate this and to provoke pain and secondary hyperalgesia we use an intradermal electrical pain model which is well established.1;7-9 Detailed description of this model look at reference 7. H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.
- Conditions
- Hyperalgesia, Secondary
- Being tested
- Placebo, Remifentanil, Ketorolac and remifentanil, Parecoxib and remifentanil
- Keywords
- hyperalgesia, remifentanil, ketorolac, parecoxib, COX-1 inhibitor, COX-2 inhibitor
- Medical subject headings
- Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Placebo IV before placebo infusion
RemifentanilDrug
Also called Ultiva
placebo IV and remifentanil infusion
Ketorolac and remifentanilDrug
Also called Toradol
Ketorolac IV and remifentanil infusion
Parecoxib and remifentanilDrug
Also called Dynastat
Parecoxib IV and remifentanil infusion
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
| Remifentanil | Active comparator | Not described Receives: Drug: Remifentanil |
| Ketorolac and remifentanil | Active comparator | Not described Receives: Drug: Ketorolac and remifentanil |
| Parecoxib and remifentanil | Active comparator | Not described Receives: Drug: Parecoxib and remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi.
Measured: during the study
Secondary outcomes (1)
HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.
Measured: During the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2008 (estimated)
- Study startDec 2008
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyperalgesia, SecondaryStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ullevaal University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oslo, Rikshospitalet University Hospital
- Investigators
- Harald Lenz, MD, Principal investigator, Ullevaal University HospitalJohan Raeder, Prof.,MD,PhD, Study director, Ullevaal University HospitalAudun Stubhaug, Prof.,MD,PhD, Study director, Rikshospitalet University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00785863
- Sponsor's protocol ID
- 2008-000904-10
- Other IDs
- 2008
- Status last verified
- Nov 2008
- First submitted
- 4 Nov 2008
- Last updated
- 1 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans
- ClinicalTrials.gov ID
- NCT00785863
- Acronym / sponsor ID
- 2008-000904-10
- Conditions
- Hyperalgesia, Secondary
- Keywords
- hyperalgesia, remifentanil, ketorolac, parecoxib, COX-1 inhibitor, COX-2 inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Ullevaal University HospitalUniversity, hospital or other
- Collaborators
- University of Oslo, Rikshospitalet University Hospital
- Study start
- Dec 2008
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 5 Nov 2008 (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.
In addition to alleviate pain there is growing evidence that µ-opioids enhance pain. This problem is known as opioid induced hyperalgesia(OIH).The NMDA receptor is involved in opioid induced hyperalgesia it may be possible to block OIH by cyclooxygenase inhibitors. This has been demonstrated with parecoxib, a COX-II inhibitor, in a experimental pain model.Both COX-1 and COX-2 are expressed in the spinal cord. It would be of interest to investigate whether a COX-1 preferring inhibitor like ketorolac also can reduce opioid induced hyperalgesic in this experimental pain model.
Detailed description
Remifentanil is an fast acting opioid which has become very popular to use during surgery.
There are studies, both experimental 1-3 and clinical 4;5, which indicate that remifentanil after end of infusion trigger enhanced pain experience and enhanced opioid consumption postoperatively.
Therefore it is important to look at possibilities to block this enhanced pain experience (opioid induced hyperalgesia - OIH). Ketamin has demonstrated to block this effect 5;6 through the NMDA receptor. Unfortunately ketamin has some seriously side-effects like hallucinations, and is therefore not suitable in ordenary clinical use.
Recently, it has been demonstrated that parecoxib (a COX-2 inhibitor) can prevent remifentanil-induced postinfusion hyperalgesia in a study on healthy volunteers.7 COX-2 inhibitors have some disadvantages because of the longterm adverse effects like cardiac arrest. Therefore it would be of interest to look at a COX-1 preferring NSAID, like ketorolac, to see if also non-selective NSAIDs can partly block remifentanil-induced postinfusion hyperalgesia.
To investigate this and to provoke pain and secondary hyperalgesia we use an intradermal electrical pain model which is well established.1;7-9 Detailed description of this model look at reference 7. H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placebo |
| Remifentanil | Active comparator | Drug: Remifentanil |
| Ketorolac and remifentanil | Active comparator | Drug: Ketorolac and remifentanil |
| Parecoxib and remifentanil | Active comparator | Drug: Parecoxib and remifentanil |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy volunteers
Key exclusion criteria (1 listed)
- Allergy to the drugs used in the study
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 |
|---|---|---|
| PlaceboPlacebo IV before placebo infusion | Other | Placebo |
| RemifentanilAlso: Ultivaplacebo IV and remifentanil infusion | Drug | Remifentanil |
| Ketorolac and remifentanilAlso: ToradolKetorolac IV and remifentanil infusion | Drug | Ketorolac and remifentanil |
| Parecoxib and remifentanilAlso: DynastatParecoxib IV and remifentanil infusion | Drug | Parecoxib and remifentanil |
Primary outcome
H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi.
Time frame: during the study
1 secondary outcome
HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.
Time frame: During the study
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 1 Jul 2011.
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.
Harald Lenz, MD principal investigator
Ullevaal University Hospital
Johan Raeder, Prof.,MD,PhD study director
Ullevaal University Hospital
Audun Stubhaug, Prof.,MD,PhD study director
Rikshospitalet 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 4 study testing Remifentanil, Ketorolac and remifentanil and Parecoxib and remifentanil in people with Hyperalgesia, Secondary, 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 1 inclusion and 1 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 1 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. 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 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?
H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi. (time frame: during the study). 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 1 Jul 2011.