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Scoliosis CorrectionPhase 4NCT05718544

Mini-dose Esketamine-dexmedetomidine Supplemented Analgesia and Long-term Outcomes

A Phase 4 study testing Esketamine, Dexmedetomidine and Sufentanil in people with Scoliosis Correction and Postoperative Analgesia, run by Peking University First Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Chronic postsurgical pain (CPSP) refers to pain that occurs or increases after surgery and lasts longer than 3 months. Severe postoperative acute pain is one of the major risk factors of CPSP. Spine surgery brings severe postoperative pain due to large trauma and long duration. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Esketamine, Dexmedetomidine and Sufentanil
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
199 participants
Where
1 siteChina
Study dates
30 Jan 2023to 7 Sep 2023
Phase
Phase 4
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged ≥18 years;
  • Scheduled for scoliosis correction surgery;
  • Required patient-controlled intravenous analgesia (PCIA) after surgery.

Who cannot join

  • Preoperative sick sinus syndrome, severe sinus bradycardia (heart rate <50 beats per minute), atrioventricular block grade II or above without pacemaker, congenital heart disease, arrhythmia, or other serious cardiovascular diseases with a New York Heart Association class ≥III;
  • Obstructive sleep apnea syndrome, or a STOP-Bang score ≥3 in combination with a serum bicarbonate level ≥28 mmol/L;
  • Comorbid hyperthyroidism or pheochromocytoma;
  • History of schizophrenia, epilepsy, myasthenia gravis;
  • Preoperative delirium or communication barrier;
  • Severe liver dysfunction (Child-Pugh grade C), severe renal dysfunction (preoperative dialysis), or American Society of Anaesthesiologists grade ≥IV;
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  • Body weight <40 kg;
  • Enrolled in other clinical studies;
  • Loss to follow-up;
  • Other conditions that were considered unsuitable for study participation.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking University First Hospital

    Beijing, Beijing Municipality, 100034

Other trials in China

About this study

Official title: Effect of Mini-dose Esketamine-dexmedetomidine Supplemented Analgesia on Long-term Outcomes Following Scoliosis Correction Surgery: 2-year Follow-up of a Randomized Controlled Trial

Chronic postsurgical pain (CPSP) refers to pain that occurs or increases after surgery and lasts longer than 3 months. Severe postoperative acute pain is one of the major risk factors of CPSP. Spine surgery brings severe postoperative pain due to large trauma and long duration. Ketamine and esketamine are N-methyl-D-aspartate receptor antagonists; they have anti-hyperalgesic effects and may reduce CPSP. Dexmedetomidine is an alpha 2-adrenoceptor agonist with sedative, anxiolytic, and analgesic effect; it is frequently used as an adjuvant to postoperative analgesia. In a previous trial of the investigators, 200 patients following scoliosis correction surgery were randomzied to receive opioid analgsia supplemented with either mini-dose esketamine-dexmedetomidine combination or placebo. The results showed that esketamine-dexmedetomidine supplement analgesia significantly improved analgesia and sleep quality after surgery. This study is designed to test the hypothesis that mini-dose esketamine-dexmedetomidine supplemented analgesia may reduce CPSP at 2 years after scoliosis correction surgery.

Read the detailed description

Chronic postsurgical pain (CPSP) refers to pain that occurs or increases after surgery and lasts longer than 3 months. Pain can be limited to the surgical area or projected to the innervated area. The incidence of CPSP is about 10-50%, and the incidence of moderate to severe CPSP is as high as 11.8%. The risk factors of CPSP include severe postoperative acute pain, long duration surgery, and related nerve injury. Spine surgery brings severe lesion and postoperative pain due to large trauma and long duration, with a median pain score of 7 (interquaritle range, 4 to 8) on the first day after surgery. And the incidence of persistent pain is as high as 75%.

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptors are located in the brain and spinal cord of the central nervous system, responsible for the afferent of noxious stimuli. After nerve injury, the continuous activity and transmission of nociceptive signals up-regulates NMDA receptors in the dorsal horn of the spinal cord, amplify the pain signal to the brain, which may be related to the pathogenesis of CPSP. Ketamine has anti-hyperalgesia effects and may reduce the occurrence of CPSP by blocking NMDA receptors. Esketamine is the S-enantiomer of racemic ketamine with stronger analgesic effect and lower incidence of adverse reactions. In previous studies, opioid-dependent patients who received low-dose ketamine/esketamine infusion during the perioperative period had decreased pain scores and opioid requirement at 6 weeks, 6 months, and 1 year after surgery. However, results of patients without opioid dependence are controversial. In addition, ketamine/esketamine are approved for refractory depression. There is a significant correlation between anxiety/depression and chronic pain. This may also be one of the mechanisms in preventing CPSP.

Dexmedetomidine is a highly selective α2 receptor agonist with sedative, anxiolytic, and analgesic effects. It can improve analgesic effect, reduce opioid consumption, and reduce opioid-related adverse reactions when used in the perioperative period. Meanwhile, dexmedetomidine can prolong total sleep time, improve sleep efficiency, and increase subjective sleep quality, possibly by activating the endogenous sleep pathway. The sedative effect of dexmedetomidine may help to reduce the psychiatric adverse reactions of ketamine. However, data is lacking regarding the effect of dexmedetomidine on chronic postsurgical pain.

In a previous trial of the investigators, 200 patients following scoliosis correction surgery were randomzied to receive opioid analgsia supplemented with either mini-dose esketamine-dexmedetomidine combination or placebo. The results showed that esketamine-dexmedetomidine supplement analgesia significantly reduced the incidence of moderate and severe pain and improved the quality of sleep during the perioperative period; adverse reactions were not significantly increased (unpublished data). This study is designed to test the hypothesis that mini-dose esketamine-dexmedetomidine supplemented analgesia may reduce CPSP at 2 years after scoliosis correction surgery.

Being tested
Esketamine, Dexmedetomidine, Sufentanil
Keywords
Scoliosis Correction, Postoperative analgesia, Esketamine, Dexmedetomidine, 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

    Esketamine 50 mg is included in the mixture for patient-controlled analgesia.

  • DexmedetomidineDrug

    Dexmedetomidine 200 microgram is included in the mixture for patient-controlled analgesia.

  • SufentanilDrug

    Sufentanil 4 microgram/kg (maximum 250 microgram) is included in the mixture for patient-controlled analgesia.

Study groups in NCT05718544
Study groupRoleWhat they receive
Combined supplementExperimentalPatient-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; Drug: Dexmedetomidine; Drug: Sufentanil
PlaceboPlacebo comparatorPatient-controlled analgesia is established with sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lock-out interval of 8 minutes and a background infusion rate at 1 ml/h.
Receives: Drug: Sufentanil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of chronic postsurgical pain at 2 years after surgery

    Chronic postsurgical pain (CPSP) is defined as pain persisted for at least three months after surgery, that is not present before surgery or that has different characteristics, and other possible causes of the pain are excluded (e.g., cancer recurrence, infection).

    Measured: At 2 years after surgery

Secondary outcomes (8)

  1. Severity of chronic pain at 2 years after surgery

    Severity of chronic pain is assessed with the Brief Pain Inventory (BPI). The BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score is calculated from the four items about pain intensity. Each item is rated from 0, no pain, to 10, pain as bad as you can imagine, and contributes with the same weight to the final score, ranging from 0 to 40.

    Measured: At 2 years after surgery

  2. Interference of chronic pain at 2 years after surgery

    Interference of chronic pain is assessed with the Brief Pain Inventory (BPI). The BPI gives two main scores: a pain severity score and a pain interference score. The pain interference score corresponds to the item on pain interference. The seven subitems are rated from 0, does not interfere, to 10, completely interferes, and contributes with the same weight to the final score, ranging from 0 to 70.

    Measured: At 2 years after surgery

  3. Proportion of chronic analgesic use after surgery

    Chronic analgesic use is defined as consecutive use of analgesics for more than 3 months.

    Measured: Up to 2 years after surgery

  4. Proportion of analgesic use at 2 years after surgery

    Proportion of analgesic use at 2 years after surgery (consecutive use of analgesics for more than 1 week within 3 months).

    Measured: At 2 years after surgery

  5. Subjective sleep quality at 2 years after surgery

    Subjective sleep quality at 2 years is assessed with the Pittsburgh Sleep Quality Index (PSQI). PSQI is a 7-item questionnaire consisting 19 self-rated questions that assesses sleep quality over the last month, each weighted equally on a 0-3 scale; higher scores indicate worse sleep quality.

    Measured: At 2 years after surgery

  6. Depression severity at 2 years after surgery

    Depression is assessed with the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 includes 9-item requiring responses of 0 (not at all) to 3 (nearly every day) to assess the occurrence of depressive symptoms over the last two weeks. It has 8 items on depressive symptoms and 1 focused on suicidal ideation. Total scores range from 0 to 27, with higher score indicating more severe symptoms.

    Measured: At 2 years after surgery

  7. Quality of life at 2 years after surgery

    Quality of life is assessed using the Scoliosis Research Society-22 (SRS-22) patient questionnaire, which consists of five domains: function, pain, mental health, self-image, and satisfaction with management.

    Measured: At 2 years after surgery

  8. Event-free survival

    Event indicates any condition that requires hospitalization and clinical treatment for unexpected reasons.

    Measured: Up to 2 years after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2023
  2. Study start30 Jan 2023
  3. Primary completion7 Sep 2023
  4. Study completion7 Sep 2023

Resources

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
199 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05718544
Sponsor's protocol ID
2023-017
Status last verified
Jul 2025
First submitted
30 Jan 2023
Last updated
30 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Willis DE, Goldstein PA. Targeting Affective Mood Disorders With Ketamine to Prevent Chronic Postsurgical Pain. Front Pain Res (Lausanne). 2022 Jun 27;3:872696. doi: 10.3389/fpain.2022.872696. eCollection 2022.

    PubMed 35832728

  • Fletcher D, Stamer UM, Pogatzki-Zahn E, Zaslansky R, Tanase NV, Perruchoud C, Kranke P, Komann M, Lehman T, Meissner W; euCPSP group for the Clinical Trial Network group of the European Society of Anaesthesiology. Chronic postsurgical pain in Europe: An observational study. Eur J Anaesthesiol. 2015 Oct;32(10):725-34. doi: 10.1097/EJA.0000000000000319.

    PubMed 26241763

  • Wylde 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 28681962

  • 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 23392233

  • Hussain 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 23374545

  • Dunn 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 29570151

  • Leider 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 21348566

  • Agarwal D, Chahar P, Chmiela M, Sagir A, Kim A, Malik F, Farag E. Multimodal Analgesia for Perioperative Management of Patients presenting for Spinal Surgery. Curr Pharm Des. 2019;25(19):2123-2132. doi: 10.2174/1381612825666190708174639.

    PubMed 31298146

  • Bartova L, Papageorgiou K, Milenkovic I, Dold M, Weidenauer A, Willeit M, Winkler D, Kasper S. Rapid antidepressant effect of S-ketamine in schizophrenia. Eur Neuropsychopharmacol. 2018 Aug;28(8):980-982. doi: 10.1016/j.euroneuro.2018.05.007. Epub 2018 Jul 2.

    PubMed 30041987

  • Molero 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 29736744

  • Canuso 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 29656663

  • Segmiller 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 23893490

  • Loftus 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 20693876

  • Nielsen 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 28067693

  • Nielsen 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 30246357

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Esketamine, Dexmedetomidine and Sufentanil in people with Scoliosis Correction and Postoperative Analgesia, run by Peking University First 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 10 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 30 Jul 2025. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of chronic postsurgical pain at 2 years after surgery (time frame: At 2 years 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 NCT05718544, which also lists 26 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 30 Jul 2025.

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