Postoperative PainNCT04643132
S-ketamine Prevents Postoperative Pain and Cognitive Dysfunction After Tibial Fracture
A study testing Normal saline, S-ketamine (low-dose) and S-ketamine (high-dose) in people with Postoperative Pain and Postoperative Cognitive Dysfunction, run by Tianjin Medical University General Hospital at 1 site in China.
Trial summary
Purpose: To explore effects of S-ketamine on postoperative pain and cognitive dysfunction after tibial fracture and orthopedic surgery. 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 65 to 85 years
- Conditions the study is for
- Postoperative Pain, Postoperative Cognitive Dysfunction
- What is being tested?
- Normal saline, S-ketamine (low-dose) and S-ketamine (high-dose)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 15 Dec 2020to 15 Dec 2021
- Phase
- Interventional
- 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 65 to 85 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Subject is scheduled to undergo tibial fracture with orthopedic 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 bronchial asthma, coronary heart disease, severe hypertension, renal failure or liver failure.
- Subject has a diagnosis of Insulin dependent diabetes.
- Subject is allergy and contraindication to S-ketamine.
- Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre- existing therapy with opioids.
- 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).
- Subject is incapacity to comprehend pain assessment and cognitive assessment.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Tianjin Medical University General Hospital
Tianjin, 300052
Guolin Wang, +8615822855556, wangguolinghad@hotmail.com
About this study
Official title: S-ketamine Prevents Tibial Fracture-associated Postoperative Pain and Cognitive Dysfunction After Orthopedic Surgery in Patients: a Randomized Double-blind Controlled Trial
Purpose:
To explore effects of S-ketamine on postoperative pain and cognitive dysfunction after tibial fracture and orthopedic surgery.
To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.
Read the detailed description
With the increase in human life span, orthopedic injuries and subsequent repair surgery have become a major health problem which impairs the life quality of patients and burdens healthcare systems worldwide. Poor post-surgical pain control is a leading factor that hinders the physical rehabilitation and musculoskeletal functional recovery, and causes acute cognitive impairment and chronic pain syndrome. Also, existing treatments of opioids and non-steroidal anti-inflammatory drugs have potential drawbacks, which may in turn interfere with bone healing. Therefore, prophylaxis of fracture-associated pain is indispensable to postoperative comfort and satisfaction.
There is no denying the fact that pathologic pain is related to central glutaminergic system and N-methyl-d-aspartate (NMDA) receptor activation induced central sensitization. Also, we previously reported that neuroinflammation is associated with pain development and cognitive dysfunction. Ketamine, a NMDA receptor antagonist, is effective in reversing NMDA receptor activation underlying pain states. But the side effects of ketamine limit its clinical application, such as Delirium, gibberish and agitation. It is clarified that S-ketamine has lower side effects than ketamine and that antinociception of S-ketamine is stronger than ketamine. The following study is carried out to evaluate whether S-ketamine can prevent postoperative pain and cognitive impairment after tibial fracture and orthopedic surgery in patients.
- Being tested
- Normal saline, S-ketamine (low-dose), S-ketamine (high-dose)
- Keywords
- S-ketamine, tibial fracture, orthopedic surgery, pain intensity
- Medical subject headings
- Pain, Postoperative, Postoperative Cognitive Complications, Tibial Fractures, Pain
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
After the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20ml/h normal saline until starting skin suture.
S-ketamine (low-dose)Drug
Also called Esketamine Hydrochloride Injection
After the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture.
S-ketamine (high-dose)Drug
Also called Esketamine Hydrochloride Injection
After the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture.
| Study group | Role | What they receive |
|---|---|---|
| Normal saline in patients | Placebo comparator | After the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20 ml/h normal saline until starting skin suture. Receives: Drug: Normal saline |
| S-ketamine at low dose in patients | Active comparator | After the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture. Receives: Drug: S-ketamine (low-dose) |
| S-ketamine at high dose in patients | Active comparator | After the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture. Receives: Drug: S-ketamine (high-dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mechanical hyperalgesia threshold on the palms of feet
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.
Measured: 48 hours after surgery
Secondary outcomes (7)
Pain Score (NRS)
The pain score at rest or after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.
Measured: 48 hours after surgery
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
Measured: 48 hours after surgery
Time of First Postoperative Analgesic Requirement
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
Measured: 1 hour after surgery
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 (Patient-controlled analgesia) pump containing sufentanil (100μg) in normal saline at a total volume of 100 ml after leaving PACU (Postanesthesia 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 48 hours postoperatively
Measured: 48 hours after surgery
Occurrence of Side Effects
Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus
Measured: 48 hours after surgery
Mini-Mental State Examination (MMSE)
Cognitive performance was assessed with Mini-Mental State Examination (MMSE).
Measured: 48 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 posted24 Nov 2020
- Study start15 Dec 2020
- Primary completion15 Nov 2021 (estimated)
- Study completion15 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postoperative 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
- 120 participants (estimated)
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
- NCT04643132
- Sponsor's protocol ID
- GWang011
- Status last verified
- Aug 2021
- First submitted
- 17 Nov 2020
- Last updated
- 13 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhang L, Terrando N, Xu ZZ, Bang S, Jordt SE, Maixner W, Serhan CN, Ji RR. Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice. Front Pharmacol. 2018 May 1;9:412. doi: 10.3389/fphar.2018.00412. eCollection 2018.
PubMed 29765320Cui W, Li Y, Wang Z, Song C, Yu Y, Wang G, Li J, Wang C, Zhang L. Spinal caspase-6 regulates AMPA receptor trafficking and dendritic spine plasticity through netrin-1 in postoperative pain after orthopedic surgery for tibial fracture in mice. Pain. 2021 Jan;162(1):124-134. doi: 10.1097/j.pain.0000000000002021.
PubMed 32701657
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- S-ketamine Prevents Tibial Fracture-associated Postoperative Pain and Cognitive Dysfunction After Orthopedic Surgery in Patients: a Randomized Double-blind Controlled Trial
- ClinicalTrials.gov ID
- NCT04643132
- Acronym / sponsor ID
- GWang011
- Keywords
- S-ketamine, tibial fracture, orthopedic surgery, pain intensity
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Tianjin Medical University General HospitalUniversity, hospital or other
- Study start
- 15 Dec 2020 (actual)
- Primary completion
- 15 Nov 2021 (estimated)
- Study completion
- 15 Dec 2021 (estimated)
- First posted
- 24 Nov 2020 (actual)
- 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.
Purpose:
To explore effects of S-ketamine on postoperative pain and cognitive dysfunction after tibial fracture and orthopedic surgery.
To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.
Detailed description
With the increase in human life span, orthopedic injuries and subsequent repair surgery have become a major health problem which impairs the life quality of patients and burdens healthcare systems worldwide. Poor post-surgical pain control is a leading factor that hinders the physical rehabilitation and musculoskeletal functional recovery, and causes acute cognitive impairment and chronic pain syndrome. Also, existing treatments of opioids and non-steroidal anti-inflammatory drugs have potential drawbacks, which may in turn interfere with bone healing. Therefore, prophylaxis of fracture-associated pain is indispensable to postoperative comfort and satisfaction.
There is no denying the fact that pathologic pain is related to central glutaminergic system and N-methyl-d-aspartate (NMDA) receptor activation induced central sensitization. Also, we previously reported that neuroinflammation is associated with pain development and cognitive dysfunction. Ketamine, a NMDA receptor antagonist, is effective in reversing NMDA receptor activation underlying pain states. But the side effects of ketamine limit its clinical application, such as Delirium, gibberish and agitation. It is clarified that S-ketamine has lower side effects than ketamine and that antinociception of S-ketamine is stronger than ketamine. The following study is carried out to evaluate whether S-ketamine can prevent postoperative pain and cognitive impairment after tibial fracture and orthopedic surgery in patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Normal saline in patients | Placebo comparator | Drug: Normal salineAfter the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20 ml/h normal saline until starting skin suture. |
| S-ketamine at low dose in patients | Active comparator | Drug: S-ketamine (low-dose)After the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture. |
| S-ketamine at high dose in patients | Active comparator | Drug: S-ketamine (high-dose)After the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture. |
Who may qualify
- Ages
- 65 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- Subject is scheduled to undergo tibial fracture with orthopedic 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 (8 listed)
- Subject has a diagnosis of bronchial asthma, coronary heart disease, severe hypertension, renal failure or liver failure.
- Subject has a diagnosis of Insulin dependent diabetes.
- Subject is allergy and contraindication to S-ketamine.
- Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre- existing therapy with opioids.
- 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 InjectionAfter the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20ml/h normal saline until starting skin suture. | Drug | Normal saline in patients |
| S-ketamine (low-dose)Also: Esketamine Hydrochloride InjectionAfter the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture. | Drug | S-ketamine at low dose in patients |
| S-ketamine (high-dose)Also: Esketamine Hydrochloride InjectionAfter the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture. | Drug | S-ketamine at high dose in patients |
Primary outcome
Mechanical hyperalgesia threshold on the palms of feet
Time frame: 48 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.
7 secondary outcomes
Pain Score (NRS)
Time frame: 48 hours after surgery
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm
Time frame: 48 hours after surgery
Time of First Postoperative Analgesic Requirement
Time frame: 1 hour after surgery
Total Dose of First Postoperative Analgesic Requirement
Time frame: 1 hour after surgery
Cumulative Sufentanyl Consumption
Time frame: 48 hours after surgery
Occurrence of Side Effects
Time frame: 48 hours after surgery
Mini-Mental State Examination (MMSE)
Time frame: 48 hours after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2021.
- Background: PubMed 29765320Zhang L, Terrando N, Xu ZZ, Bang S, Jordt SE, Maixner W, Serhan CN, Ji RR. Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice. Front Pharmacol. 2018 May 1;9:412. doi: 10.3389/fphar.2018.00412. eCollection 2018.
- Background: PubMed 32701657Cui W, Li Y, Wang Z, Song C, Yu Y, Wang G, Li J, Wang C, Zhang L. Spinal caspase-6 regulates AMPA receptor trafficking and dendritic spine plasticity through netrin-1 in postoperative pain after orthopedic surgery for tibial fracture in mice. Pain. 2021 Jan;162(1):124-134. doi: 10.1097/j.pain.0000000000002021.
- 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.
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, S-ketamine (low-dose) and S-ketamine (high-dose) in people with Postoperative Pain and Postoperative Cognitive Dysfunction, 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 8 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: status not confirmed, as of the sponsor's last update on 13 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guolin Wang, MD (+8615822855556, wangguolinghad@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mechanical hyperalgesia threshold on the palms of feet (time frame: 48 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 NCT04643132, which also lists 2 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 13 Aug 2021; AzTrials last refreshed its copy on 6 Nov 2026.