HyperalgesiaPhase 4NCT02992938
Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia
A Phase 4 study testing Acetazolamide in people with Hyperalgesia and Opioid-Related Disorders, run by University of Chile at 1 site in Chile.
Trial summary
Remifentanil is a potent opioid widely used during the administration of general anesthesia. There is a lot of evidence that suggest that the used of remifentanil is associated with the development of hyperalgesia (a reduction of nociceptive thresholds). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperalgesia, Opioid-Related Disorders
- What is being tested?
- Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteChile
- Study dates
- Dec 2016to 28 Sep 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients scheduled for thyroidectomy with general anesthesia in the University of Chile Clinical Hospital
Who cannot join
- Patients ASA III y IV
- Chronic pain history
- Drug and alcohol abuse
- Chronic use of opioid and sedatives
- Neuropsychiatric illness
- NSAID and other analgesics used the 48 hours previous to the surgery
- CMI > 30
Trial locations and contacts
1 site in 1 country.
Chile1 site
Faculty of Medicine, University of Chile
Santiago, Santiago Metropolitan, 7563215
About this study
Official title: Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia: Randomize Double Blind Clinical Trial
Remifentanil is a potent opioid widely used during the administration of general anesthesia. There is a lot of evidence that suggest that the used of remifentanil is associated with the development of hyperalgesia (a reduction of nociceptive thresholds). However, the mechanism of this hyperalgesia is not fully understood.
Recently, it was demonstrated that the disruption of the Cl- homeostasis could be involved. Interestingly, this was prevented in a murine model with the administration of Acetazolamide, a carbonic anhydrase inhibitor. In our clinical trial we will try to determine if the preoperative administration of acetazolamide could prevent the hyperalgesia induced by remifentanil in patients scheduled for thyroidectomy with general anesthesia.
- Conditions
- Hyperalgesia, Opioid-Related Disorders
- Being tested
- Acetazolamide, Placebo Oral Tablet
- Keywords
- Opioid hyperalgesia, Acetazolamide, Remifentanil
- Medical subject headings
- Hyperalgesia, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
Placebo Oral TabletDrug
| Study group | Role | What they receive |
|---|---|---|
| Acetazolamide | Experimental | 250 mg VO of acetazolamide will be administered the day of the surgery 2 hours before anesthesia induction Receives: Drug: Acetazolamide |
| Placebo | Placebo comparator | An oral tablet without active principle acetazolamide but with the same physical characteristics will be administered the day of the surgery 2 hours before anesthesia induction Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the mechanical pain threshold in an area distant to the site of the injury
The threshold will be determine using von Frey monofilaments before the surgery and will be compared 12-18 hours after the end of the surgery
Measured: 12-18 hours after the end of the surgery
Secondary outcomes (3)
Change in the mechanical pain threshold in an area distant to the site of the injury
Measured: 2 hours after the end of the surgery
Postoperative pain
A visual analogue scale (VAS; 0, no pain; 100, worst poss- ible pain) will be used to assess pain
Measured: The first postoperative day
Morphine consumption
Morphine consumption with a patient controlled analgesia (PCA) in mg
Measured: The first postoperative day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2016 (estimated)
- Study startDec 2016
- Primary completion28 Sep 2018
- Study completion28 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HyperalgesiaStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chile
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rodrigo Gutiérrez, University of Chile
- Investigators
- Rodrigo Gutierrez, MD, Principal investigator, Anesthesia Department, University of ChileAntonello Penna, MD PhD, Principal investigator, Anesthesia Department, University of Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02992938
- Sponsor's protocol ID
- 803/16
- Status last verified
- Dec 2018
- First submitted
- 11 Dec 2016
- Last updated
- 31 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ferrini F, Trang T, Mattioli TA, Laffray S, Del'Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci. 2013 Feb;16(2):183-92. doi: 10.1038/nn.3295. Epub 2013 Jan 6.
PubMed 23292683Echevarria G, Elgueta F, Fierro C, Bugedo D, Faba G, Iniguez-Cuadra R, Munoz HR, Cortinez LI. Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans. Br J Anaesth. 2011 Dec;107(6):959-65. doi: 10.1093/bja/aer323. Epub 2011 Sep 28.
PubMed 21965050Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003 Nov;106(1-2):49-57. doi: 10.1016/s0304-3959(03)00276-8.
PubMed 14581110Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, Chauvin M. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005 Jul;103(1):147-55. doi: 10.1097/00000542-200507000-00022.
PubMed 15983467
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia: Randomize Double Blind Clinical Trial
- ClinicalTrials.gov ID
- NCT02992938
- Acronym / sponsor ID
- 803/16
- Conditions
- Hyperalgesia, Opioid-Related Disorders
- Keywords
- Opioid hyperalgesia, Acetazolamide, Remifentanil
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of ChileUniversity, hospital or other
- Study start
- Dec 2016 (actual)
- Primary completion
- 28 Sep 2018 (actual)
- Study completion
- 28 Sep 2018 (actual)
- First posted
- 14 Dec 2016 (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.
Remifentanil is a potent opioid widely used during the administration of general anesthesia. There is a lot of evidence that suggest that the used of remifentanil is associated with the development of hyperalgesia (a reduction of nociceptive thresholds). However, the mechanism of this hyperalgesia is not fully understood.
Recently, it was demonstrated that the disruption of the Cl- homeostasis could be involved. Interestingly, this was prevented in a murine model with the administration of Acetazolamide, a carbonic anhydrase inhibitor. In our clinical trial we will try to determine if the preoperative administration of acetazolamide could prevent the hyperalgesia induced by remifentanil in patients scheduled for thyroidectomy with general anesthesia.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Experimental | Drug: Acetazolamide250 mg VO of acetazolamide will be administered the day of the surgery 2 hours before anesthesia induction |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletAn oral tablet without active principle acetazolamide but with the same physical characteristics will be administered the day of the surgery 2 hours before anesthesia induction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients scheduled for thyroidectomy with general anesthesia in the University of Chile Clinical Hospital
Key exclusion criteria (7 listed)
- Patients ASA III y IV
- Chronic pain history
- Drug and alcohol abuse
- Chronic use of opioid and sedatives
- Neuropsychiatric illness
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 |
|---|---|---|
| Acetazolamide | Drug | Acetazolamide |
| Placebo Oral Tablet | Drug | Placebo |
Primary outcome
Change in the mechanical pain threshold in an area distant to the site of the injury
Time frame: 12-18 hours after the end of the surgery
The threshold will be determine using von Frey monofilaments before the surgery and will be compared 12-18 hours after the end of the surgery
3 secondary outcomes
Change in the mechanical pain threshold in an area distant to the site of the injury
Time frame: 2 hours after the end of the surgery
Postoperative pain
Time frame: The first postoperative day
Morphine consumption
Time frame: The first postoperative day
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 31 Dec 2018.
- Results publication: PubMed 23292683Ferrini F, Trang T, Mattioli TA, Laffray S, Del'Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci. 2013 Feb;16(2):183-92. doi: 10.1038/nn.3295. Epub 2013 Jan 6.
- Results publication: PubMed 21965050Echevarria G, Elgueta F, Fierro C, Bugedo D, Faba G, Iniguez-Cuadra R, Munoz HR, Cortinez LI. Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans. Br J Anaesth. 2011 Dec;107(6):959-65. doi: 10.1093/bja/aer323. Epub 2011 Sep 28.
- Results publication: PubMed 14581110Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003 Nov;106(1-2):49-57. doi: 10.1016/s0304-3959(03)00276-8.
- Results publication: PubMed 15983467Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, Chauvin M. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005 Jul;103(1):147-55. doi: 10.1097/00000542-200507000-00022.
- Individual participant dataSharing planned: No
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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.
Rodrigo Gutierrez, MD principal investigator
Anesthesia Department, University of Chile
Antonello Penna, MD PhD principal investigator
Anesthesia Department, University of Chile
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 Acetazolamide in people with Hyperalgesia and Opioid-Related Disorders, run by University of Chile at 1 site in Chile.
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 7 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 31 Dec 2018. 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 Chile. 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?
Change in the mechanical pain threshold in an area distant to the site of the injury (time frame: 12-18 hours after the end of the surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02992938, which also lists 4 linked publications.
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 31 Dec 2018.