Postoperative PainNCT05132595
Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty
A study testing Normal saline, Esketamine at high dose and Esketamine at low 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 compare esketamine and ketorolac separately and in combination to prevent postoperative pain and cognitive dysfunction after total knee arthroplasty Read more about this study
- Who is it for?
- Ages 65 to 85 years
- Conditions the study is for
- Postoperative Pain, Postoperative Cognitive Dysfunction, Total Knee Arthroplasty
- What is being tested?
- Normal saline, Esketamine at high dose and Esketamine at low dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 30 Nov 2021to 30 Jul 2022
- 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 total knee arthroplasty 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 esketamine or ketorolac.
- 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, +8618604755166
About this study
Official title: Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty in Patients: a Randomized Double-blind Controlled Trial
Purpose:
To compare esketamine and ketorolac separately and in combination to prevent postoperative pain and cognitive dysfunction after total knee arthroplasty
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. Therefore, prophylaxis of postoperative 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, it is 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 gibberish and agitation. It is clarified that esketamine has lower side effects than ketamine and that antinociception of esketamine is stronger than ketamine. The following study is carried out to evaluate whether esketamine and ketorolac can prevent postoperative pain and cognitive impairment after total knee arthroplasty in patients.
- Being tested
- Normal saline, Esketamine at high dose, Esketamine at low dose, Ketorolac at high dose, Ketorolac at low dose
- Keywords
- esketamine, ketorolac
- Medical subject headings
- Pain, Postoperative, Postoperative Cognitive Complications
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.
Esketamine at high doseDrug
Also called Esketamine Hydrochloride Injection
After the induction of anesthesia, esketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h esketamine until starting skin suture.
Esketamine at low doseDrug
Also called Esketamine Hydrochloride Injection
After the induction of anesthesia, esketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h esketamine until starting skin suture.
Ketorolac at high doseDrug
Also called Ketorolac Tromethamine
After the induction of anesthesia, Ketorolac is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h Ketorolac until starting skin suture.
Ketorolac at low doseDrug
Also called Ketorolac Tromethamine
After the induction of anesthesia, Ketorolac is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h Ketorolac 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 |
| Esketamine in patients | Active comparator | After the induction of anesthesia, esketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h esketamine until starting skin suture. Receives: Drug: Esketamine at high dose |
| Ketorolac in patients | Active comparator | After the induction of anesthesia, ketorolac is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h ketorolac until starting skin suture. Receives: Drug: Ketorolac at high dose |
| Esketamine and Ketorolac in patients | Active comparator | After the induction of anesthesia, 0.2mg/kg esketamine and 0.2mg/kg ketorolac are intravenously injected, and then a continuous infusion of 0.2mg/kg/h esketamine and 0.2mg/kg/h ketorolac until starting skin suture. Receives: Drug: Esketamine at low dose; Drug: Ketorolac at low dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative opioid Consumption
Each patient was administered analgesics using a PCA (Patient-controlled analgesia) pump containing sufentanil in normal saline after leaving PACU (Postanesthesia care unit). Sufentanyl cumulative consumption is recorded 72 hours postoperatively
Measured: 72 hours after surgery
Secondary outcomes (15)
Pain Score (NRS) after movement
The pain score after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.
Measured: 72 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
Mini-Mental State Examination (MMSE)
Cognitive performance was assessed with 0-30 points Mini-Mental State Examination (MMSE) scale. Greater scores means better outcome.
Measured: 72 hours after surgery
The incidence of Side Effects
The number of patients with post-operative side effects including nausea, vomiting, dizziness, headache, shivering, and pruritus was recorded 72 hours after surgery.
Measured: 72 hours after surgery
The levels of TNF-a in blood
Blood samples are collected to measure the levels of cytokine TNF-a using ELISA kits.
Measured: 72 hours after surgery
The levels of chemokine CXCL1 in blood
Blood samples are collected to measure the levels of chemokine CXCL1 using ELISA kits.
Measured: 72 hours after surgery
The levels of neuron specific enolase (NSE) in blood
Blood samples are collected to measure the levels of neuron specific enolase (NSE) using electrochemilumiscence kit.
Measured: 72 hours after surgery
The levels of S-100 calcium-binding protein B in blood
Blood samples are collected to measure the levels of S-100 calcium-binding protein B using electrochemilumiscence kit.
Measured: 72 hours after surgery
The levels of cortisol in blood
Blood samples are collected to measure the levels of cortisol using electrochemilumiscence kit.
Measured: 72 hours after surgery
Pain Score (NRS) at rest
The pain score at rest was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.
Measured: 72 hours after surgery
The levels of chemokine CCL7 in blood
Blood samples are collected to measure the levels of chemokine CCL7 using ELISA kits.
Measured: 72 hours after surgery
The levels of IL-18 in blood
Blood samples are collected to measure the levels of cytokine IL-18 using ELISA kits.
Measured: 72 hours after surgery
The levels of IL-23 in blood
Blood samples are collected to measure the levels of cytokine IL-23 using ELISA kits.
Measured: 72 hours after surgery
The levels of IL-17 in blood
Blood samples are collected to measure the levels of cytokine IL-17 using ELISA kits.
Measured: 72 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 2021
- Study start30 Nov 2021
- Primary completion15 Jul 2022 (estimated)
- Study completion30 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 160 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, Principal investigator, Tianjin Medical University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05132595
- Sponsor's protocol ID
- GWang020
- Status last verified
- Apr 2022
- First submitted
- 28 Oct 2021
- Last updated
- 15 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Esketamine vs. Ketorolac for Prevention of Postoperative Pain and Cognitive Dysfunction After Total Knee Arthroplasty in Patients: a Randomized Double-blind Controlled Trial
- ClinicalTrials.gov ID
- NCT05132595
- Acronym / sponsor ID
- GWang020
- Keywords
- esketamine, ketorolac
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Tianjin Medical University General HospitalUniversity, hospital or other
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 15 Jul 2022 (estimated)
- Study completion
- 30 Jul 2022 (estimated)
- First posted
- 24 Nov 2021 (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 compare esketamine and ketorolac separately and in combination to prevent postoperative pain and cognitive dysfunction after total knee arthroplasty
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. Therefore, prophylaxis of postoperative 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, it is 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 gibberish and agitation. It is clarified that esketamine has lower side effects than ketamine and that antinociception of esketamine is stronger than ketamine. The following study is carried out to evaluate whether esketamine and ketorolac can prevent postoperative pain and cognitive impairment after total knee arthroplasty in patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| 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. |
| Esketamine in patients | Active comparator | Drug: Esketamine at high doseAfter the induction of anesthesia, esketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h esketamine until starting skin suture. |
| Ketorolac in patients | Active comparator | Drug: Ketorolac at high doseAfter the induction of anesthesia, ketorolac is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h ketorolac until starting skin suture. |
| Esketamine and Ketorolac in patients | Active comparator | Drug: Esketamine at low dose, Drug: Ketorolac at low doseAfter the induction of anesthesia, 0.2mg/kg esketamine and 0.2mg/kg ketorolac are intravenously injected, and then a continuous infusion of 0.2mg/kg/h esketamine and 0.2mg/kg/h ketorolac 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 total knee arthroplasty 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 esketamine or ketorolac.
- 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 |
| Esketamine at high doseAlso: Esketamine Hydrochloride InjectionAfter the induction of anesthesia, esketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h esketamine until starting skin suture. | Drug | Esketamine in patients |
| Esketamine at low doseAlso: Esketamine Hydrochloride InjectionAfter the induction of anesthesia, esketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h esketamine until starting skin suture. | Drug | Esketamine and Ketorolac in patients |
| Ketorolac at high doseAlso: Ketorolac TromethamineAfter the induction of anesthesia, Ketorolac is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h Ketorolac until starting skin suture. | Drug | Ketorolac in patients |
| Ketorolac at low doseAlso: Ketorolac TromethamineAfter the induction of anesthesia, Ketorolac is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h Ketorolac until starting skin suture. | Drug | Esketamine and Ketorolac in patients |
Primary outcome
Cumulative opioid Consumption
Time frame: 72 hours after surgery
Each patient was administered analgesics using a PCA (Patient-controlled analgesia) pump containing sufentanil in normal saline after leaving PACU (Postanesthesia care unit). Sufentanyl cumulative consumption is recorded 72 hours postoperatively
15 secondary outcomes
Pain Score (NRS) after movement
Time frame: 72 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
Mini-Mental State Examination (MMSE)
Time frame: 72 hours after surgery
The incidence of Side Effects
Time frame: 72 hours after surgery
The levels of TNF-a in blood
Time frame: 72 hours after surgery
The levels of chemokine CXCL1 in blood
Time frame: 72 hours after surgery
The levels of neuron specific enolase (NSE) in blood
Time frame: 72 hours after surgery
The levels of S-100 calcium-binding protein B in blood
Time frame: 72 hours after surgery
The levels of cortisol in blood
Time frame: 72 hours after surgery
Pain Score (NRS) at rest
Time frame: 72 hours after surgery
The levels of chemokine CCL7 in blood
Time frame: 72 hours after surgery
The levels of IL-18 in blood
Time frame: 72 hours after surgery
The levels of IL-23 in blood
Time frame: 72 hours after surgery
The levels of IL-17 in blood
Time frame: 72 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 15 Apr 2022.
- 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 principal investigator
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, Esketamine at high dose and Esketamine at low 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 15 Apr 2022. 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?
Cumulative opioid Consumption (time frame: 72 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 15 Apr 2022.