Modulation of Remifentanil-induced Postinfusion Hyperalgesia

Hyperalgesia, Secondary Clinical Trial

Official title:

Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00785863
• Other study ID #: 2008-000904-10
• Status: Completed
• Phase: Phase 4
• First received: November 4, 2008
• Last updated: June 30, 2011
• Start date: December 2008
• Est. completion date: April 2009

Study information

• Verified date: November 2008
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway:National Committee for Medical and Health Research EthicsNorway: Norwegian Medicines AgencyNorway: Norwegian Social Science Data ServicesNorway: Directorate of Health
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Allergy to the drugs used in the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hyperalgesia
• Hyperalgesia, Secondary

Intervention

Other:
• Placebo
Placebo IV before placebo infusion

Drug:
• Remifentanil
placebo IV and remifentanil infusion
• Ketorolac and remifentanil
Ketorolac IV and remifentanil infusion
• Parecoxib and remifentanil
Parecoxib IV and remifentanil infusion

Locations

Country	Name	City	State
Norway	Ullevaal University Hospital	Oslo

Sponsors (3)

Lead Sponsor	Collaborator
Ullevaal University Hospital	Rikshospitalet University Hospital, University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi.		during the study	No
Secondary	HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.		During the study	No