PainNCT02043366
Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Hyperalgesia Induced by Remifentanil in Patients
A study testing Normal Saline, Butorphanol and Flurbiprofen axetil in people with Pain and Anesthesia, run by Tianjin Medical University General Hospital at 1 site in China.
Trial summary
Purpose: To explore and compare antihyperalgesic effects of butorphanol, flurbiprofen axetil, and a combination of both received before anesthesia induction. To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose. . Read more about this study
- Who is it for?
- Ages 20 to 60 years
- Conditions the study is for
- Pain, Anesthesia
- What is being tested?
- Normal Saline, Butorphanol and Flurbiprofen axetil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 1 siteChina
- Study dates
- Feb 2014to Aug 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subject is scheduled to undergo lower abdominal surgery under a short general anesthesia of less than 2 hours
- Subject's American Society of Anesthesiologists physical status is I-II.
- The subject's parent/legally authorized guardian has given written informed consent to participate.
Who cannot join
- Subject has a diagnosis of renal or liver failure.
- Subject has a diagnosis of Insulin dependent diabetes.
- Subject is allergy and contraindication to butorphanol or NSAIDs.
- Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre-existing therapy with opioids, intake of any analgesic drug within 48 hours before surgery.
- Subject has any contraindication for the use of patient-controlled analgesia (PCA).
- Subject is pregnant or breast-feeding.
- Subject is obese (body mass index >30kg/m^2).
Trial locations and contacts
1 site in 1 country.
China1 site
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
About this study
Official title: Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Postoperative Hyperalgesia Induced by Remifentanil in Patients Undergoing Lower Abdomimal Surgery
Purpose:
To explore and compare antihyperalgesic effects of butorphanol, flurbiprofen axetil, and a combination of both received before anesthesia induction.
To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.
.
Read the detailed description
There are a dramatically increasing number of evidences that administration of the potent, ultra-short-acting opioid remifentanil seems to cause opioid-induced hyperalgesia (OIH) more frequently and predictably compared with the others, likely due to its rapid onset and offset. Therefore, prophylaxis of remifentanil induced hyperalgesia is indispensable to postoperative comfort and satisfaction.
There is no denying the fact that OIH is related to central glutaminergic system and N-methyl-d-aspartate (NMDA) receptor-activation induced central sensitization. Prostaglandins can promote glutamate release from both astrocytes and spinal cord dorsal horns with subsequent activation of the NMDA receptors, and flurbiprofen axetil, as non-steroidal anti-inflammatory drugs (NSAIDs), not only functionally antagonizes the NMDA receptor activation via inhibition of prostaglandins, but also is a targeted drug which gathers at the site of inflammation, thus greatly enhances the analgesic effect. While butorphanol has both spinal analgesic and sedative functions because of predominantly central κ-receptor agonist activation, other advantages of butorphanol include few side effects, very low addiction potential, and low toxicity on account of a partial agonist-antagonist activity to μ-receptor. Moreover, antihyperalgesic activity of κ opioids at the site of inflammation has been reported in various acute pain models. The following study is carried out to evaluate whether butorphanol combined with flurbiprofen axetil can be safely and effectively applied to preventing postoperative hyperalgesia induced by remifentanil in patients undergoing lower abdominal surgery.
- Conditions
- Pain, Anesthesia
- Being tested
- Normal Saline, Butorphanol, Flurbiprofen axetil, Remifentanil, Sufentanil
- Keywords
- Remifentanil, Opioid-induced hyperalgesia, Postoperative pain, Pain Intensity
- Medical subject headings
- Pain, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal SalineDrug
Normal Saline is intravenously administrated before anesthesia induction
ButorphanolDrug
Butorphanol is intravenously administrated
Flurbiprofen axetilDrug
Flurbiprofen axetil is intravenously administrated
RemifentanilDrug
Remifentanil is intravenously administrated
SufentanilDrug
Sufentanil is intravenously administrated
| Study group | Role | What they receive |
|---|---|---|
| Normal Saline | Placebo comparator | Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Receives: Drug: Normal Saline; Drug: Remifentanil |
| Butorphanol | Active comparator | Butorphanol is intravenously administrated at a dose of 20μg/ kg before anesthesia induction and intraoperative pain management was with remifentanil Receives: Drug: Butorphanol; Drug: Remifentanil |
| Flurbiprofen axetilⅠ | Active comparator | Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before anesthesia induction and intraoperative pain management was with remifentanil Receives: Drug: Flurbiprofen axetil; Drug: Remifentanil |
| Flurbiprofen axetilⅡ | Active comparator | Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before the skin closure and intraoperative pain management was with remifentanil Receives: Drug: Flurbiprofen axetil; Drug: Remifentanil |
| Butorphanol-Flurbiprofen axetil | Active comparator | A dose of 10μg/ kg butorphanol and a dose of 0.5mg/ kg flurbiprofen axetil are intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Receives: Drug: Butorphanol; Drug: Flurbiprofen axetil; Drug: Remifentanil |
| Sufentanil | Sham comparator | Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with sufentanil Receives: Drug: Normal Saline; Drug: Sufentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm
The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament at 24 hours postoperatively
Measured: 24 hours after surgery
Secondary outcomes (6)
Pain Score (NRS)
The pain score at rest was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.
Measured: 3h, 6h, 12h, and 24h after surgery
Time of First Postoperative Analgesic Requirement
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
Measured: 1 hour post surgery
Occurrence of Side Effects
Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus
Measured: 24 hours
Total Dose of First Postoperative Analgesic Requirement
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
Measured: 1 hour after surgery
Cumulative Sufentanyl Consumption
Each patient was administered analgesics using a PCA pump containing sufentanil (100μg) in normal saline at a total volume of 100 ml after leaving PACU. This device was set to deliver a basal infusion of 2 ml/h and bolus doses of 0.5 ml with a 15-min lockout period. Sufentanyl cumulative consumption is recorded 24 hours postoperatively
Measured: 24 hours
Normalized Area of Hyperalgesia Around the Incision
The skin around the incision is stimulated in steps of 5 mm at intervals of 1 s starting outside of the hyperalgesic area in the direction of the incision. The distance from the incision to the first point where a 'painful', 'sore' or 'sharper' feeling occurred is measured and noted. This measurement is repeated at predefined radial lines around the incision. To eliminate the variable length of incision, this length is subtracted from the longer diameter leaving four radial distances from the end and from the middle of the incision. The normalized area of hyperalgesia is calculated by summing up the areas of the remaining four triangles measured by and Von Frey filament.
Measured: 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionJun 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guolin Wang, Tianjin Medical University General Hospital
- Investigators
- Guolin Wang, MD, Study director, Tianjin Medical University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02043366
- Sponsor's protocol ID
- GWang001
- Status last verified
- Dec 2015
- First submitted
- 15 Jan 2014
- Last updated
- 8 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Zhang L, Shu R, Zhao Q, Li Y, Yu Y, Wang G. Preoperative butorphanol and flurbiprofen axetil therapy attenuates remifentanil-induced hyperalgesia after laparoscopic gynaecological surgery: a randomized double-blind controlled trial. Br J Anaesth. 2016 Oct;117(4):504-511. doi: 10.1093/bja/aew248. Epub 2016 Oct 17.
PubMed 28077539
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Postoperative Hyperalgesia Induced by Remifentanil in Patients Undergoing Lower Abdomimal Surgery
- ClinicalTrials.gov ID
- NCT02043366
- Acronym / sponsor ID
- GWang001
- Conditions
- Pain, Anesthesia
- Keywords
- Remifentanil, Opioid-induced hyperalgesia, Postoperative pain, Pain Intensity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Tianjin Medical University General HospitalUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 23 Jan 2014 (estimated)
- Results
- Posted 28 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose:
To explore and compare antihyperalgesic effects of butorphanol, flurbiprofen axetil, and a combination of both received before anesthesia induction.
To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.
.
Detailed description
There are a dramatically increasing number of evidences that administration of the potent, ultra-short-acting opioid remifentanil seems to cause opioid-induced hyperalgesia (OIH) more frequently and predictably compared with the others, likely due to its rapid onset and offset. Therefore, prophylaxis of remifentanil induced hyperalgesia is indispensable to postoperative comfort and satisfaction.
There is no denying the fact that OIH is related to central glutaminergic system and N-methyl-d-aspartate (NMDA) receptor-activation induced central sensitization. Prostaglandins can promote glutamate release from both astrocytes and spinal cord dorsal horns with subsequent activation of the NMDA receptors, and flurbiprofen axetil, as non-steroidal anti-inflammatory drugs (NSAIDs), not only functionally antagonizes the NMDA receptor activation via inhibition of prostaglandins, but also is a targeted drug which gathers at the site of inflammation, thus greatly enhances the analgesic effect. While butorphanol has both spinal analgesic and sedative functions because of predominantly central κ-receptor agonist activation, other advantages of butorphanol include few side effects, very low addiction potential, and low toxicity on account of a partial agonist-antagonist activity to μ-receptor. Moreover, antihyperalgesic activity of κ opioids at the site of inflammation has been reported in various acute pain models. The following study is carried out to evaluate whether butorphanol combined with flurbiprofen axetil can be safely and effectively applied to preventing postoperative hyperalgesia induced by remifentanil in patients undergoing lower abdominal surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Normal Saline | Placebo comparator | Drug: Normal Saline, Drug: RemifentanilNormal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil |
| Butorphanol | Active comparator | Drug: Butorphanol, Drug: RemifentanilButorphanol is intravenously administrated at a dose of 20μg/ kg before anesthesia induction and intraoperative pain management was with remifentanil |
| Flurbiprofen axetilⅠ | Active comparator | Drug: Flurbiprofen axetil, Drug: RemifentanilFlurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before anesthesia induction and intraoperative pain management was with remifentanil |
| Flurbiprofen axetilⅡ | Active comparator | Drug: Flurbiprofen axetil, Drug: RemifentanilFlurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before the skin closure and intraoperative pain management was with remifentanil |
| Butorphanol-Flurbiprofen axetil | Active comparator | Drug: Butorphanol, Drug: Flurbiprofen axetil, Drug: RemifentanilA dose of 10μg/ kg butorphanol and a dose of 0.5mg/ kg flurbiprofen axetil are intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil |
| Sufentanil | Sham comparator | Drug: Normal Saline, Drug: SufentanilNormal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with sufentanil |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Subject is scheduled to undergo lower abdominal surgery under a short general anesthesia of less than 2 hours
- Subject's American Society of Anesthesiologists physical status is I-II.
- The subject's parent/legally authorized guardian has given written informed consent to participate.
Key exclusion criteria (7 listed)
- Subject has a diagnosis of renal or liver failure.
- Subject has a diagnosis of Insulin dependent diabetes.
- Subject is allergy and contraindication to butorphanol or NSAIDs.
- Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre-existing therapy with opioids, intake of any analgesic drug within 48 hours before surgery.
- Subject has any contraindication for the use of patient-controlled analgesia (PCA).
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 |
|---|---|---|
| Normal SalineNormal Saline is intravenously administrated before anesthesia induction | Drug | Normal Saline, Sufentanil |
| ButorphanolButorphanol is intravenously administrated | Drug | Butorphanol, Butorphanol-Flurbiprofen axetil |
| Flurbiprofen axetilFlurbiprofen axetil is intravenously administrated | Drug | Butorphanol-Flurbiprofen axetil, Flurbiprofen axetilⅠ, Flurbiprofen axetilⅡ |
| RemifentanilRemifentanil is intravenously administrated | Drug | Butorphanol, Butorphanol-Flurbiprofen axetil, Flurbiprofen axetilⅠ, Flurbiprofen axetilⅡ, Normal Saline |
| SufentanilSufentanil is intravenously administrated | Drug | Sufentanil |
Primary outcome
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm
Time frame: 24 hours after surgery
The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament at 24 hours postoperatively
6 secondary outcomes
Pain Score (NRS)
Time frame: 3h, 6h, 12h, and 24h after surgery
Time of First Postoperative Analgesic Requirement
Time frame: 1 hour post surgery
Occurrence of Side Effects
Time frame: 24 hours
Total Dose of First Postoperative Analgesic Requirement
Time frame: 1 hour after surgery
Cumulative Sufentanyl Consumption
Time frame: 24 hours
Normalized Area of Hyperalgesia Around the Incision
Time frame: 24 hours after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28077539Zhang L, Shu R, Zhao Q, Li Y, Yu Y, Wang G. Preoperative butorphanol and flurbiprofen axetil therapy attenuates remifentanil-induced hyperalgesia after laparoscopic gynaecological surgery: a randomized double-blind controlled trial. Br J Anaesth. 2016 Oct;117(4):504-511. doi: 10.1093/bja/aew248. Epub 2016 Oct 17.
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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.
Guolin Wang, MD study director
Tianjin Medical University General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Normal Saline, Butorphanol and Flurbiprofen axetil in people with Pain and Anesthesia, run by Tianjin Medical University General Hospital at 1 site in China.
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 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 8 Jan 2016. 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 China. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm (time frame: 24 hours after 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 NCT02043366, which also lists 1 linked publication.
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 8 Jan 2016.