Scoliosis CorrectionPhase 4NCT06062550
Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery
A Phase 4 study testing Esketamine in people with Scoliosis Correction and Esketamine, run by Peking University First Hospital at 1 site in China.
Trial summary
Scoliosis correction surgery is associated with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and drug tolerance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Scoliosis Correction, Esketamine, Dexmedetomidine
- What is being tested?
- Esketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 312 participants
- Where
- 1 siteChina
- Study dates
- 24 Oct 2023to Oct 2026
- Phase
- Phase 4
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
- Aged ≥18 years and body weight ≥40 kg;
- Scheduled to undergo scoliosis correction with pedicle screw fixation;
- Required patient-controlled intravenous analgesia after surgery.
Who cannot join
- Preoperative sick sinus syndrome, severe sinus bradycardia (heart rate <50 beats/min), atrioventricular block grade II or above without pacemaker; or comorbid with congenital heart disease, arrhythmia, or other serious cardiovascular diseases with a cardiac function grade ≥III;
- Patients with moderate and severe obstructive sleep apnea diagnosed preoperatively or according to the STOP-Bang score；
- History of hyperthyroidism and pheochromocytoma;
- History of schizophrenia, epilepsy, myasthenia gravis, or delirium;
- Severe liver dysfunction (child Pugh grade C), severe renal dysfunction (preoperative dialysis), or American Society of Anesthesiologists grade ≥IV;
- Barrier in communication;
- Other conditions that are considered unsuitable for study participation.
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing University First Hospital
Beijing, Beijing Municipality, 100034
About this study
Official title: Efficacy of Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery: A Randomized, Double-blind Trial
Scoliosis correction surgery is associated with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and drug tolerance. In a recent trial, mini-dose esketamine and dexmedetomidine combination as a supplement to sufentanil significantly improved analgesia and subjective sleep quality after spinal correction surgery without increasing adverse events; however, the proportion of patients with moderate-to-severe pain remained high. The authors speculate that increasing esketamine dose in the combination may further improve analgesic effects.
Read the detailed description
Spinal surgery is associated with severe pain, with a median pain score of 7 (interquartile range, 4 to 8) on the first postoperative day, and requires long duration analgesia. The total dose of opioids required for postoperative analgesia is about 2-4 times that for other surgeries. However, despite high dose opioids, the analgesic effects remain unsatisfied. In a recent trial of 200 patients following scoliosis correction surgery, the proportion with moderate-to-severe pain in patients given routine analgesia was 84.6%. Severe acute pain is an important risk factor of chronic postsurgical pain and is associated with an increased risk of long-term opioid use.
Ketamine is a non-competitive N-methyl-D-aspartate receptor antagonist. Low-dose ketamine infusion is recommended for postoperative analgesia but may cause neuropsychiatric side effects. Esketamine is the S-enantiomer of racemic ketamine with approximately twice as potent as racemic ketamine in analgesia and less likely to produce side effects. Dexmedetomidine is a highly selective α2 receptor agonist and has anxiolytic, sedative, analgesic effects. When used as a supplement to opioid analgesia, dexmedetomidine improves analgesia and sleep quality but may produce sedation.
In a recent trial, mini-dose esketamine-dexmedetomidine combination as a supplement to sufentanil significantly improved analgesia and subjective sleep quality after scoliosis correction surgery; no significant adverse reactions were observed. However, the proportion of moderate-to-severe pain remained high (65.7%) in these patients, so further improvement is needed. The authors speculate that increasing esketamine dose in the esketamine-dexmedetomidine combination may further improve the analgesia. This study aims to explore the effects of different dose esketamine in the combination on acute and chronic pain in patients following spinal deformity surgery.
- Conditions
- Scoliosis Correction, Esketamine, Dexmedetomidine, Postoperative Analgesia, Chronic Postsurgical Pain
- Being tested
- Esketamine
- Keywords
- Scoliosis Correction, Esketamine, Dexmedetomidine, Postoperative Analgesia, Chronic Postsurgical Pain
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsketamineDrug
Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.
| Study group | Role | What they receive |
|---|---|---|
| Low-dose group | Active comparator | Patient-controlled analgesia is established with esketamine 50 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h. Receives: Drug: Esketamine |
| Medium-dose group | Experimental | Patient-controlled analgesia is established with esketamine 100 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h. Receives: Drug: Esketamine |
| High-dose group | Experimental | Patient-controlled analgesia is established with esketamine 150 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h. Receives: Drug: Esketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity with movement and opioid consumption within 72 hours.
A comprehensive index of pain intensity and opioid consumption is calculated. The range of the index is -200% to +200%; values above 0 indicate increased summed area under curve (AUC) and opioid consumption (OC) compared to the all patients.
Measured: Within 72 hours after surgery
Secondary outcomes (8)
Proportion of patients with moderate to severe pain within 72 hours.
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement. Moderate to severe pain is defined as any NRS pain score of 4 or higher.
Measured: Up to 72 hours after surgery.
The highest NRS pain score within 72 hours after surgery.
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement.
Measured: Up to 72 hours after surgery.
Area under curve of NRS pain score within 72 hours after surgery.
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement.
Measured: Up to 72 hours after surgery
Cumulative opioid consumption within 72 hours after surgery.
Cumulative opioid consumption within 72 hours after surgery.
Measured: Up to 72 hours after surgery
Requirement of supplement analgesia within 72 hours.
Requirement of supplement analgesia within 72 hours.
Measured: Up to 72 hours after surgery
Pain intensity at rest and opioid consumption within 72 hours.
A comprehensive index of pain intensity and opioid consumption is calculated. The range of the index is -200% to +200%; values above 0 indicate increased summed AUC and OC compared to the all patients.
Measured: Within 72 hours after surgery.
Subjective sleep quality during the first 5 postoperative days.
Subjective sleep quality is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = the best sleep and 10 = no sleep at all) once daily (8:00-10:00).
Measured: Up to the 5th day after surgery.
Number of days requiring analgesics within 30 days after surgery.
Number of days requiring analgesics within 30 days after surgery.
Measured: Up to 30 days after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2023
- Study start24 Oct 2023
- Primary completion23 Oct 2025
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Scoliosis CorrectionStudies 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
- 312 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University First Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dong-Xin Wang, Peking University First Hospital
- Investigators
- Dong-Xin Wang, MD,PhD, Principal investigator, Peking University First Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06062550
- Sponsor's protocol ID
- 2023-351
- Status last verified
- Apr 2026
- First submitted
- 25 Sep 2023
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013 Apr;118(4):934-44. doi: 10.1097/ALN.0b013e31828866b3.
PubMed 23392233Hussain A, Erdek M. Interventional pain management for failed back surgery syndrome. Pain Pract. 2014 Jan;14(1):64-78. doi: 10.1111/papr.12035. Epub 2013 Feb 3.
PubMed 23374545Wylde V, Dennis J, Beswick AD, Bruce J, Eccleston C, Howells N, Peters TJ, Gooberman-Hill R. Systematic review of management of chronic pain after surgery. Br J Surg. 2017 Sep;104(10):1293-1306. doi: 10.1002/bjs.10601. Epub 2017 Jul 6.
PubMed 28681962Dunn LK, Yerra S, Fang S, Hanak MF, Leibowitz MK, Tsang S, Durieux ME, Nemergut EC, Naik BI. Incidence and Risk Factors for Chronic Postoperative Opioid Use After Major Spine Surgery: A Cross-Sectional Study With Longitudinal Outcome. Anesth Analg. 2018 Jul;127(1):247-254. doi: 10.1213/ANE.0000000000003338.
PubMed 29570151Leider HL, Dhaliwal J, Davis EJ, Kulakodlu M, Buikema AR. Healthcare costs and nonadherence among chronic opioid users. Am J Manag Care. 2011 Jan;17(1):32-40.
PubMed 21348566Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.
PubMed 29870457Cohen SP, Bhatia A, Buvanendran A, Schwenk ES, Wasan AD, Hurley RW, Viscusi ER, Narouze S, Davis FN, Ritchie EC, Lubenow TR, Hooten WM. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):521-546. doi: 10.1097/AAP.0000000000000808.
PubMed 29870458Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sanchez E, Gutierrez-Rojas L, Meana JJ. Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS Drugs. 2018 May;32(5):411-420. doi: 10.1007/s40263-018-0519-3.
PubMed 29736744Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Am J Psychiatry. 2018 Jul 1;175(7):620-630. doi: 10.1176/appi.ajp.2018.17060720. Epub 2018 Apr 16.
PubMed 29656663Segmiller F, Ruther T, Linhardt A, Padberg F, Berger M, Pogarell O, Moller HJ, Kohler C, Schule C. Repeated S-ketamine infusions in therapy resistant depression: a case series. J Clin Pharmacol. 2013 Sep;53(9):996-8. doi: 10.1002/jcph.122. Epub 2013 Jul 24. No abstract available.
PubMed 23893490Persson J, Hasselstrom J, Maurset A, Oye I, Svensson JO, Almqvist O, Scheinin H, Gustafsson LL, Almqvist O. Pharmacokinetics and non-analgesic effects of S- and R-ketamines in healthy volunteers with normal and reduced metabolic capacity. Eur J Clin Pharmacol. 2002 Feb;57(12):869-75. doi: 10.1007/s002280100353.
PubMed 11936706Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, Beach ML. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010 Sep;113(3):639-46. doi: 10.1097/ALN.0b013e3181e90914.
PubMed 20693876Nielsen RV, Fomsgaard JS, Siegel H, Martusevicius R, Nikolajsen L, Dahl JB, Mathiesen O. Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial. Pain. 2017 Mar;158(3):463-470. doi: 10.1097/j.pain.0000000000000782.
PubMed 28067693Nielsen RV, Fomsgaard JS, Nikolajsen L, Dahl JB, Mathiesen O. Intraoperative S-ketamine for the reduction of opioid consumption and pain one year after spine surgery: A randomized clinical trial of opioid-dependent patients. Eur J Pain. 2019 Mar;23(3):455-460. doi: 10.1002/ejp.1317. Epub 2018 Oct 14.
PubMed 30246357Nielsen RV. Adjuvant analgesics for spine surgery. Dan Med J. 2018 Mar;65(3):B5468.
PubMed 29510816