Modulation of Remifentanil-induced Postinfusion Hyperalgesia

This study has been completed.
Sponsor:
Collaborators:
University of Oslo
Rikshospitalet University Hospital
Information provided by:
Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT00785863
First received: November 4, 2008
Last updated: June 30, 2011
Last verified: November 2008
  Purpose

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.


Condition Intervention Phase
Hyperalgesia, Secondary
Other: Placebo
Drug: Remifentanil
Drug: Ketorolac and remifentanil
Drug: Parecoxib and remifentanil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi. [ Time Frame: during the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi. [ Time Frame: During the study ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: December 2008
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Other: Placebo
Placebo IV before placebo infusion
Other Name: Placebo
Active Comparator: Remifentanil Drug: Remifentanil
placebo IV and remifentanil infusion
Other Name: Ultiva
Active Comparator: Ketorolac and remifentanil Drug: Ketorolac and remifentanil
Ketorolac IV and remifentanil infusion
Other Name: Toradol
Active Comparator: Parecoxib and remifentanil Drug: Parecoxib and remifentanil
Parecoxib IV and remifentanil infusion
Other Name: Dynastat

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • Allergy to the drugs used in the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00785863

Locations
Norway
Ullevaal University Hospital
Oslo, Norway, 0407
Sponsors and Collaborators
Ullevaal University Hospital
University of Oslo
Rikshospitalet University Hospital
Investigators
Principal Investigator: Harald Lenz, MD Ullevaal University Hospital
Study Director: Johan Raeder, Prof.,MD,PhD Ullevaal University Hospital
Study Director: Audun Stubhaug, Prof.,MD,PhD Rikshospitalet University Hospital
  More Information

No publications provided

Responsible Party: Ullevaal University Hospital
ClinicalTrials.gov Identifier: NCT00785863     History of Changes
Other Study ID Numbers: 2008-000904-10
Study First Received: November 4, 2008
Last Updated: June 30, 2011
Health Authority: Norway:National Committee for Medical and Health Research Ethics
Norway: Norwegian Medicines Agency
Norway: Norwegian Social Science Data Services
Norway: Directorate of Health

Keywords provided by Oslo University Hospital:
hyperalgesia
remifentanil
ketorolac
parecoxib
COX-1 inhibitor
COX-2 inhibitor

Additional relevant MeSH terms:
Hyperalgesia
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Ketorolac
Ketorolac Tromethamine
Parecoxib
Remifentanil
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Analgesics, Opioid
Central Nervous System Depressants
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on April 14, 2014