PainNCT03096730
Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia
A study testing Normal saline, Remifentanil and Sufentanil in people with Pain and Anesthesia, run by Tianjin Medical University General Hospital at 1 site in China.
Trial summary
To explore and compare antihyperalgesic effects of Dexmedetomidine,Nalmefene,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 65 years, women only
- Conditions the study is for
- Pain, Anesthesia
- What is being tested?
- Normal saline, Remifentanil and Sufentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteChina
- Study dates
- 6 Feb 2017to 30 Dec 2017
- 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 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients are scheduled to undergo Gynecological surgery under a short general anesthesia of 1-3 hours.
- American Society of Anesthesiologists physical status is I-II.
- Written informed consent was obtained from all the subjects.
Who cannot join
- Subject has a diagnosis of Coronary heart disease, bronchial asthma, cardiac, lung, hepatic and renal insufficiency.
- Subject has a diagnosis of Severe high blood pressure , diabetes, obesity (BMI>30).
- 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 h before surgery.
- .Subject has Pregnancy, psychiatric disease.
- Subject has any contraindication for the use of patient-controlled analgesia (PCA).
- Inability to understand the Study Information Sheet and provide a written consent to take part in the study.
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: The Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia in Patients Undergoing Gynecological Surgery
To explore and compare antihyperalgesic effects of Dexmedetomidine,Nalmefene,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. Dexmedetomidine is an 2-adrenergic agonist that has been shown to synergize with opioids. Dexmedetomidine inhibits NMDAR excitability by reducing the phosphorylation of N-methyl-D-aspartate receptor 2B subunit phosphorylation of spinal dorsal horn induced by remifentanil, thereby achieving the goal of reducing OIH. Nalmefene is a pure opioid receptor antagonist that antagonizes the Mu receptor, alleviating the central sensitization of NMDA, thereby reducing OIH. At the same time reported in the literature, opioid receptor has a bimode：On the one hand can be mediated by Gs protein-mediated pain, respiratory depression, nausea and vomiting, etc ; on the other hand can be coupled with Gi / Go protein mediated analgesic effect. Low-dose nalmefene (<1.0ug / kg) and other opioid receptor antagonists can antagonize the role of Gs protein-coupled opioid receptors, blocking the pathway of opioid excitatory effects, thereby reducing the incidence of adverse reactions.The following study is carried out to evaluate whether dexmedetomidine combined with nalmefene can be safely and effectively applied to prevent postoperative hyperalgesia induced by remifentanil in patients undergoing Laparoscopic gynecological surgery.
- Conditions
- Pain, Anesthesia
- Being tested
- Normal saline, Remifentanil, Sufentanil, Dexmedetomidine injection, Nalmefene
- 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
Also called 0. 9% Sodium Chloride Injection
Normal saline is intravenously administrated before anesthesia induction
RemifentanilDrug
Also called Remifentanil Hydrochloride for Injection
Remifentanil is intravenously administrated
SufentanilDrug
Also called Sufentanil injection
Sufentanil is intravenously administrated
Dexmedetomidine injectionDrug
Also called Dexmedetomidine
Dexmedetomidine is intravenously administrated before anesthesia induction
NalmefeneDrug
Nalmefene is intravenously administrated before anesthesia induction
| 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 |
| Sufentanil | Sham comparator | Normal saline is intravenously admistrated before anesthesia induction and intraoperative pain management was with sufentanil Receives: Drug: Normal saline; Drug: Sufentanil |
| Dexmedetomidine | Active comparator | Dexmedetomidine is intravenously administrated at a dose of 0.5ug/kg 10min before anesthesia induction and intraoperative pain management was with remifentanil Receives: Drug: Remifentanil; Drug: Dexmedetomidine injection |
| Nalmefene | Active comparator | Nalmefene is intravenously administrated at a dose of 0.2ug/kg before anesthesia induction and intraoperative pain management was with remifentanil Receives: Drug: Remifentanil; Drug: Nalmefene |
| Dexmedetomidine-Nalmefene | Active comparator | A dose of 0.1ug/kg nalmefene and a dose of 0.25ug/kg dexmedetomidine for 10 minutes before anesthesia induction and intraoperative pain management was with remifentanil Receives: Drug: Remifentanil; Drug: Dexmedetomidine injection; Drug: Nalmefene |
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 (5)
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: 1hours,3hours，6hours，12hours，24hours after surgery
Pain Score (Numerical Rating Scale)
The pain score at rest was evaluated by pain 11-point numerical rating scale : 0 = no pain, 10 = greatest imaginable pain.
Measured: 1hours,3hours，6hours，12hours，24hours after surgery
Time of First Postoperative Analgesic Requirement
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
Measured: postoperative 1 hours
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 post-anaesthesia care unit . 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: 1hours,3hours，6hours，12hours，24hours after surgery
Occurrence of Side Effects
Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus，hypotention/hypertention，bradycardia/tachycardia
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2017
- Study start6 Feb 2017
- Primary completion20 Dec 2017
- Study completion30 Dec 2017
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.
- 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
- 150 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
- Wang Guolin, MD, Study director, Tianjin Medical University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03096730
- Sponsor's protocol ID
- GWang003
- Status last verified
- Aug 2021
- First submitted
- 13 Mar 2017
- Last updated
- 3 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: data not entered
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia in Patients Undergoing Gynecological Surgery
- ClinicalTrials.gov ID
- NCT03096730
- Acronym / sponsor ID
- GWang003
- Conditions
- Pain, Anesthesia
- Keywords
- Remifentanil, Opioid-induced hyperalgesia, Postoperative pain, pain intensity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Tianjin Medical University General HospitalUniversity, hospital or other
- Study start
- 6 Feb 2017 (actual)
- Primary completion
- 20 Dec 2017 (actual)
- Study completion
- 30 Dec 2017 (actual)
- First posted
- 30 Mar 2017 (actual)
- Results
- Posted 3 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To explore and compare antihyperalgesic effects of Dexmedetomidine,Nalmefene,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. Dexmedetomidine is an 2-adrenergic agonist that has been shown to synergize with opioids. Dexmedetomidine inhibits NMDAR excitability by reducing the phosphorylation of N-methyl-D-aspartate receptor 2B subunit phosphorylation of spinal dorsal horn induced by remifentanil, thereby achieving the goal of reducing OIH. Nalmefene is a pure opioid receptor antagonist that antagonizes the Mu receptor, alleviating the central sensitization of NMDA, thereby reducing OIH. At the same time reported in the literature, opioid receptor has a bimode：On the one hand can be mediated by Gs protein-mediated pain, respiratory depression, nausea and vomiting, etc ; on the other hand can be coupled with Gi / Go protein mediated analgesic effect. Low-dose nalmefene (<1.0ug / kg) and other opioid receptor antagonists can antagonize the role of Gs protein-coupled opioid receptors, blocking the pathway of opioid excitatory effects, thereby reducing the incidence of adverse reactions.The following study is carried out to evaluate whether dexmedetomidine combined with nalmefene can be safely and effectively applied to prevent postoperative hyperalgesia induced by remifentanil in patients undergoing Laparoscopic gynecological surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 5
| 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 |
| Sufentanil | Sham comparator | Drug: Normal saline, Drug: SufentanilNormal saline is intravenously admistrated before anesthesia induction and intraoperative pain management was with sufentanil |
| Dexmedetomidine | Active comparator | Drug: Remifentanil, Drug: Dexmedetomidine injectionDexmedetomidine is intravenously administrated at a dose of 0.5ug/kg 10min before anesthesia induction and intraoperative pain management was with remifentanil |
| Nalmefene | Active comparator | Drug: Remifentanil, Drug: NalmefeneNalmefene is intravenously administrated at a dose of 0.2ug/kg before anesthesia induction and intraoperative pain management was with remifentanil |
| Dexmedetomidine-Nalmefene | Active comparator | Drug: Remifentanil, Drug: Dexmedetomidine injection, Drug: NalmefeneA dose of 0.1ug/kg nalmefene and a dose of 0.25ug/kg dexmedetomidine for 10 minutes before anesthesia induction and intraoperative pain management was with remifentanil |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients are scheduled to undergo Gynecological surgery under a short general anesthesia of 1-3 hours.
- American Society of Anesthesiologists physical status is I-II.
- Written informed consent was obtained from all the subjects.
Key exclusion criteria (6 listed)
- Subject has a diagnosis of Coronary heart disease, bronchial asthma, cardiac, lung, hepatic and renal insufficiency.
- Subject has a diagnosis of Severe high blood pressure , diabetes, obesity (BMI>30).
- 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 h before surgery.
- .Subject has Pregnancy, psychiatric disease.
- 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 salineAlso: 0. 9% Sodium Chloride InjectionNormal saline is intravenously administrated before anesthesia induction | Drug | Normal Saline, Sufentanil |
| RemifentanilAlso: Remifentanil Hydrochloride for InjectionRemifentanil is intravenously administrated | Drug | Dexmedetomidine, Dexmedetomidine-Nalmefene, Nalmefene, Normal Saline |
| SufentanilAlso: Sufentanil injectionSufentanil is intravenously administrated | Drug | Sufentanil |
| Dexmedetomidine injectionAlso: DexmedetomidineDexmedetomidine is intravenously administrated before anesthesia induction | Drug | Dexmedetomidine, Dexmedetomidine-Nalmefene |
| NalmefeneNalmefene is intravenously administrated before anesthesia induction | Drug | Dexmedetomidine-Nalmefene, Nalmefene |
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
5 secondary outcomes
Normalized Area of Hyperalgesia Around the Incision
Time frame: 1hours,3hours，6hours，12hours，24hours after surgery
Pain Score (Numerical Rating Scale)
Time frame: 1hours,3hours，6hours，12hours，24hours after surgery
Time of First Postoperative Analgesic Requirement
Time frame: postoperative 1 hours
Cumulative Sufentanyl Consumption
Time frame: 1hours,3hours，6hours，12hours，24hours after surgery
Occurrence of Side Effects
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. data not entered
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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.
Wang Guolin, 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, Remifentanil and Sufentanil 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 6 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 3 Aug 2021. 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 3 Aug 2021). 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?
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 3 Aug 2021.