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S-ketaminePhase 4NCT04964219

Analgesic Effects of Low-dose S-ketamine in Major Spine Fusion Surgery

A Phase 4 study testing S-ketamine in people with S-ketamine 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

Despite opioid-based multimodal analgesia, moderate-to-severe pain remains a big problem in patients following multi-segment spinal fusion. As a N-methyl-D-aspartate receptor antagonist, S-ketamine has prominent analgesic effects through activating receptors both in the brain and in the spinal cord, inhibiting the… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
S-ketamine, Postoperative Analgesia, Spine Fusion
What is being tested?
S-ketamine
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
164 participants
Where
1 siteChina
Study dates
8 Feb 2022to 2 May 2025
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged between 18 and 80 years.
  • Scheduled to undergo multi-segment (≥2) spine fusion surgery.
  • Agreed to receive postoperative patient-controlled analgesia.

Who cannot join

  • Refused to participant in this trial.
  • Poor blood pressure control in those with hypertension (BP >160/100 mmHg in the ward).
  • Previous history of hyperthyroidism or pheochromocytoma.
  • Previous history of schizophrenia, epilepsy or Parkinson disease.
  • History of sick sinus syndrome, bradycardia (HR <50 beat per min), or atrioventricular block of grade II or higher without pacemaker.
  • Severe heart dysfunction (New York Heart Association functional classification 4), hepatic insufficiency (Child-Pugh grade C), renal insufficiency (serum creatinine of 442 μmol/L or above, or requirement of renal replacement therapy), or ASA classification IV or above.
  • Unable to complete preoperative assessment due to severe dementia or language barrier.
  • Any other conditions that were considered unsuitable for the study participation.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Beijing University First Hospital

    Beijing, Beijing Municipality, 100034

Other trials in China

About this study

Official title: Analgesic Effects of Low-dose S-ketamine in Patients Undergoing Major Spine Fusion Surgery: A Double-blinded, Randomized Controlled Trial

Despite opioid-based multimodal analgesia, moderate-to-severe pain remains a big problem in patients following multi-segment spinal fusion. As a N-methyl-D-aspartate receptor antagonist, S-ketamine has prominent analgesic effects through activating receptors both in the brain and in the spinal cord, inhibiting the excitatory postsynaptic potential, and thus blunting nociception transmission.

This randomized controlled trial is designed to investigate whether perioperative S-ketamine infusion can decrease pain intensity after major spine fusion surgery.

Read the detailed description

Multi-segment spinal fusion usually lasts long and produces significant trauma. Patients following this surgery are at high risk of developing moderate-to-severe pain. In a large sample size cohort study investigating pain severity following 179 kinds of surgical procedures, multi-segment spinal fusion ranked the third with a median pain score of 6.6 (assessed with an 11-point scale, where 0=no pain and 10= the worst pain) and a median morphine consumption of 27 mg during the first postoperative day.

High-dose opioids are associated with adverse effects including respiratory depression, sedation, nausea and vomiting, pruritus, and constipation, which are harmful for early postoperative recovery. A previous study showed that about 50% of patients are taking opioids for chronic pain at 3 months after spinal fusion surgery. Chronic pain is considered to be a result of poorly controlled acute postoperative pain. Thus, multimodal analgesia aiming at improving analgesia while decreasing opioid consumption is advocated to control acute postsurgical pain, in order to promote perioperative recovery and prevent chronic pain.

Racemic ketamine, a commonly used N-methyl-D-aspartate receptor antagonist, is a mixture of equal parts of two optical isomers including R-(-)-ketamine and S-(+)-ketamine. It has prominent analgesic effects through activating receptors both in the brain and in the spinal cord, inhibiting the excitatory postsynaptic potential, and thus blunting nociception transmission. Additionally, studies also showed that, when used within the appropriate time, ketamine reduces pain-related sensitization that aggravates postoperative pain. Thus, ketamine is recommended as a part of a multimodal analgesia regimen in clinical practice, especially for patients undergoing major orthopedic surgery. However, the reported psychotropic side effects limit the clinical use of racemic ketamine.

S-ketamine, an S-isomer of ketamine, is twice as potent as the racemic mixture in analgesia, and produces fewer side effects than the racemic ketamine. How, there are only a few studies exploring analgesic effect of S-ketamine in spine fusion surgery. In opioid-dependent patients, Nielsen et al. reported that intraoperative S-ketamine infusion reduced opioid consumption within 24 hours and relieved back pain intensity at 6 months, it also decreased the daily opioid use at 1 year after spinal surgery. On the other hand, the study of Brinck et al. did not found any superiority of intraoperative S-ketamine in reducing oxycodone consumption within 48 hours after lumbar fusion surgery in opioid-naive patients.

Considering these inconsistent results, the effects of S-ketamine in spinal surgery require further clarification. This trial is designed to investigate the analgesic effect of S-ketamine infused both intraoperatively and postoperatively in patients undergoing multi-segment spine infusion surgery.

Being tested
S-ketamine, Placebo
Keywords
S-ketamine, Postoperative Analgesia, Spine Fusion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • S-ketamineDrug

    After anesthesia induction, a bolus of 0.15 mg/kg S-ketamine is injected intravenously about 30 min before incision; this is followed by a continuous infusion at a rate of 0.15 mg/kg/h until 1 hour before the end of surgery.

    After surgery, patient-controlled analgesia is provided. The pump is established with S-ketamine 25 mg, dexmedetomidine 100 microgram, and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.

  • PlaceboDrug

    After anesthesia induction, a bolus of placebo (normal saline) in the same volume is injected intravenously about 30 min before incision; this is followed by a continuous infusion of placebo at the same rate until 1 hour before the end of surgery.

    After surgery, patient-controlled analgesia is provided. The pump is established with placebo, dexmedetomidine 100 microgram and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.

Study groups in NCT04964219
Study groupRoleWhat they receive
S-ketamine groupExperimentalAfter anesthesia induction, a bolus of 0.15 mg/kg S-ketamine is injected intravenously about 30 min before incision; this is followed by a continuous infusion at a rate of 0.15 mg/kg/h until 1 hour before the end of surgery. After surgery, patient-controlled analgesia is provided. The pump is established with S-ketamine 25 mg, dexmedetomidine 100 microgram, and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.
Receives: Drug: S-ketamine
Control groupPlacebo comparatorAfter anesthesia induction, a bolus of placebo (normal saline) in the same volume is injected intravenously about 30 min before incision; this is followed by a continuous infusion of placebo at the same rate until 1 hour before the end of surgery. After surgery, patient-controlled analgesia is provided. The pump is established with placebo, dexmedetomidine 100 microgram and sufentanil 100 microgram, diluted with normal saline to 100 ml. The pump is programmed to deliver 2-ml boluses with a background infusion rate at 1 ml /h and a 10-min lockout interval.
Receives: Drug: Placebo

What is being measured

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

  1. The percentage of patients with moderate-to-severe pain in the first 48 hours after surgery.

    Moderate-to-severe pain is defined as a numeric rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain) pain score ≥4.

    Measured: Up to 48 hours after surgery

Secondary outcomes (11)

  1. Opioid consumption during anesthesia

    Opioid consumption in equivalent-dose of sufentanil

    Measured: From induction to end of anesthesia

  2. Cumulative opioid consumption after surgery

    Opioid consumption in equivalent-dose of sufentanil

    Measured: From end of anesthesia to the 5th day after surgery

  3. NRS pain score at rest and with movement

    Pain is assessed with a numeric rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain)

    Measured: Up to postoperative day 5

  4. The percentage of using rescue analgesics

    The percentage of using rescue analgesics

    Measured: Up to postoperative day 5

  5. Subjective sleep quality

    Subjective sleep quality is assessed with NRS scale (0 indicates the best sleep and 10 indicates the worst sleep)

    Measured: Up to postoperative day 5

  6. Time to first ambulation

    Time to first ambulation

    Measured: Up to 30 days after surgery

  7. Quality of recover after surgery

    Quality of recover is assessed with the Quality of Recovery scale, a 15-item Q-15 questionnaire with score ranges from 0 to 150, with higher score indicating better recovery.

    Measured: On the third day after surgery

  8. Length of hospital stay after surgery

    Length of hospital stay after surgery

    Measured: Up to 30 days after surgery

  9. The percentage of taking oral analgesics

    The percentage of taking oral analgesics

    Measured: On the 30th day after surgery

  10. The severity of anxiety and depression

    The severity of anxiety and depression is assessed with the Hospital Anxiety and Depression Scale, a 14-item questionnaire with scores range from 0 to 21 for either anxiety or depression. Higher score indicates more severe symptom.

    Measured: On the 30th day after surgery

  11. The incidence of postoperative complications and mortality

    The incidence of postoperative complications and mortality

    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.

  1. First posted16 Jul 2021
  2. Study start8 Feb 2022
  3. Primary completion1 Apr 2025
  4. Study completion2 May 2025

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04964219
Sponsor's protocol ID
2021-272
Status last verified
Jul 2025
First submitted
6 Jul 2021
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

  • 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

  • Stein C. New concepts in opioid analgesia. Expert Opin Investig Drugs. 2018 Oct;27(10):765-775. doi: 10.1080/13543784.2018.1516204. Epub 2018 Sep 7.

    PubMed 30148648

  • Connolly J 3rd, Javed Z, Raji MA, Chan W, Kuo YF, Baillargeon J. Predictors of Long-term Opioid Use Following Lumbar Fusion Surgery. Spine (Phila Pa 1976). 2017 Sep 15;42(18):1405-1411. doi: 10.1097/BRS.0000000000002133.

    PubMed 28263225

  • Ocay DD, Li MMJ, Ingelmo P, Ouellet JA, Page MG, Ferland CE. Predicting Acute Postoperative Pain Trajectories and Long-Term Outcomes of Adolescents after Spinal Fusion Surgery. Pain Res Manag. 2020 Feb 24;2020:9874739. doi: 10.1155/2020/9874739. eCollection 2020.

    PubMed 32184913

  • Cozowicz C, Bekeris J, Poeran J, Zubizarreta N, Schwenk E, Girardi F, Memtsoudis SG. Multimodal Pain Management and Postoperative Outcomes in Lumbar Spine Fusion Surgery: A Population-based Cohort Study. Spine (Phila Pa 1976). 2020 May 1;45(9):580-589. doi: 10.1097/BRS.0000000000003320.

    PubMed 31770340

  • Walker CT, Gullotti DM, Prendergast V, Radosevich J, Grimm D, Cole TS, Godzik J, Patel AA, Whiting AC, Little A, Uribe JS, Kakarla UK, Turner JD. Implementation of a Standardized Multimodal Postoperative Analgesia Protocol Improves Pain Control, Reduces Opioid Consumption, and Shortens Length of Hospital Stay After Posterior Lumbar Spinal Fusion. Neurosurgery. 2020 Jul 1;87(1):130-136. doi: 10.1093/neuros/nyz312.

    PubMed 31414128

  • Doan LV, Wang J. An Update on the Basic and Clinical Science of Ketamine Analgesia. Clin J Pain. 2018 Nov;34(11):1077-1088. doi: 10.1097/AJP.0000000000000635.

    PubMed 29927768

  • Brinck EC, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, Kontinen V. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018 Dec 20;12(12):CD012033. doi: 10.1002/14651858.CD012033.pub4.

    PubMed 30570761

  • Park PJ, Makhni MC, Cerpa M, Lehman RA, Lenke LG. The role of perioperative ketamine in postoperative pain control following spinal surgery. J Spine Surg. 2020 Sep;6(3):591-597. doi: 10.21037/jss-19-306.

    PubMed 33102896

  • Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30.

    PubMed 28576285

  • Arendt-Nielsen L, Nielsen J, Petersen-Felix S, Schnider TW, Zbinden AM. Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain. Br J Anaesth. 1996 Nov;77(5):625-31. doi: 10.1093/bja/77.5.625.

    PubMed 8957979

  • Adams HA, Werner C. [From the racemate to the eutomer: (S)-ketamine. Renaissance of a substance?]. Anaesthesist. 1997 Dec;46(12):1026-42. doi: 10.1007/s001010050503. German.

    PubMed 9451486

  • Pfenninger E, Baier C, Claus S, Hege G. [Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]. Anaesthesist. 1994 Nov;43 Suppl 2:S68-75. German.

    PubMed 7840417

  • Adams HA, Thiel A, Jung A, Fengler G, Hempelmann G. [Studies using S-(+)-ketamine on probands. Endocrine and circulatory reactions, recovery and dream experiences]. Anaesthesist. 1992 Oct;41(10):588-96. German.

    PubMed 1332529

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing S-ketamine in people with S-ketamine 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 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: 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?

The percentage of patients with moderate-to-severe pain in the first 48 hours after surgery. (time frame: Up to 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 NCT04964219, which also lists 17 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; AzTrials last refreshed its copy on 8 Nov 2026.

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