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Scoliosis CorrectionPhase 4NCT04791059

Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Postoperative Analgesia

A Phase 4 study testing S-ketamine, 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

Scoliosis correction surgery is followed with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and even drug tolerance. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
S-ketamine, Dexmedetomidine and Sufentanil
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
200 participants
Where
1 siteChina
Study dates
9 Apr 2021to 7 Oct 2022
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

  • Age ≥ 18 years old, body weight ≥ 40 kg;
  • Scheduled to undergo scoliosis correction with pedicle screw fixation;
  • Planned to use patient-controlled intravenous analgesia after surgery.

Who cannot join

  • Refused to participate in the study;
  • 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 obstructive sleep apnea syndrome, or a STOP-Bang score ≥ 3 in combination with a serum HCO3- level ≥ 28 mmol/L;
  • 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
  • Peking University First Hospital

    Beijing, Beijing Municipality, 100034

Other trials in China

About this study

Official title: Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Patient-controlled Analgesia After Scoliosis Correction Surgery: a Randomized, Double-blind, Placebo-controlled Trial

Scoliosis correction surgery is followed with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and even drug tolerance. S-ketamine is the pure dextrorotatory enantiomer of ketamine with stronger analgesic effect and less side effects, but mental side effects is a major concern. Dexmedetomidine can be used as an analgesic supplement; it also improves sleep quality in postoperative patients. We hypothesize that low-dose ketamine and dexmedetomidine in combination with opioids may have synergistic effect in analgesia and reduce drug-related side effects. This study aims to explore the effect of low-dose of S-ketamine and dexmedetomidine in combination with opioids for postoperative patient-controlled intravenous analgesia in patients following scoliosis correction surgery.

Read the detailed description

Scoliosis correction surgery is followed with severe pain. The reported median pain score on the first day after surgery is median 7 (IQR 4, 8); with an incidence of persistent postoperative pain from 5% to 75%. Most patients undergoing this surgery are young and adolescents; they are sensitive to pain and usually require higher dose analgesics and a long duration analgesia. The total dose of opioids required for postoperative analgesia is about 2-4 times higher than that after other surgeries. But even with high dose opioids, the analgesic effect remains unsatisfied. Furthermore, high dose opioids may cause side effects such as respiratory depression, drowsiness, nausea, vomiting, skin itching, and even drug tolerance.

Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist (NMDA) with analgesic and anti-hyperalgesia effects. It is widely used for anesthesia induction in critically ill patients, pediatric anesthesia and postoperative analgesia. The advantages of ketamine include mild influence on respiratory and circulatory function, and good analgesic effect. Recent guidelines recommends the use of low-dose ketamine infusion for postoperative analgesia in patients with moderate to severe pain, in order to reduce the consumption of opioids. S-ketamine is the pure dextrorotatory enantiomer of ketamine with stronger analgesic effect and lower incidence of adverse reactions.

Dexmedetomidine is a highly selective α2 receptor agonist with effects of antianxiety, sedation and analgesia. When used as a supplement, it improves analgesic effect, and reduces opioid consumption and opioid related adverse reactions. In the same time, dexmedetomidine activates the endogenous sleep pathway and improves sleep quality by prolonging total sleep time, increasing sleep efficiency, and promoting subjective sleep quality.

It is worthy to note that ketamine can produce adverse reactions such as agitation, delirium and anxiety, and increase the incidence of hallucinations and nightmares when the given dose is slightly higher; whereas the sedative effect of dexmedetomidine may help to reduce the adverse effects of ketamine. We hypothesize that low-dose ketamine and dexmedetomidine in combination with opioids may have synergistic effects in postoperative analgesia and reduce drug-related adverse reactions.

This study aims to explore the effect of low-dose of S-ketamine and dexmedetomidine in combination with opioids for postoperative patient-controlled intravenous analgesia in patients following scoliosis correction surgery.

Being tested
S-ketamine, Dexmedetomidine, Sufentanil
Keywords
Scoliosis correction, Postoperative analgesia, S-ketamine, Dexmedetomidine, Sufentanil

What participants receive

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

  • S-ketamineDrug

    S-ketamine 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 NCT04791059
Study groupRoleWhat they receive
Combined analgesia groupExperimentalPatient-controlled analgesia is established with S-ketamine 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 lock-out interval of 8 minutes and a background infusion rate at 1 ml/h.
Receives: Drug: S-ketamine; Drug: Dexmedetomidine; Drug: Sufentanil
Control groupPlacebo 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. Percent of patients with moderate to severe pain within 72 hours

    Pain severity 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

Secondary outcomes (9)
  1. NRS pain score (at rest and with movement) at various timepoints after surgery

    Pain severity 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

  2. Cumulative opioid consumption

    Cumulative opioid consumption

    Measured: Up to 72 hours after surgery

  3. Cumulative analgesic consumption

    Cumulative analgesic consumption

    Measured: Up to 72 hours after surgery

  4. Agitation and sedation score at various timepoints after surgery

    Agitation and sedation score is evaluated with the Richmond Agitation and Sedation Scale (RASS, with scores ranging from -5 [unarousable] to +4 [combative] and 0 indicates alert and calm) twice daily (8:00-10:00 and 18:00-20:00).

    Measured: Up to the 5th day after surgery

  5. Incidence of postoperative delirium within the first 5 days

    Delirium is assessed with the Three-dimensional Confusion Assessment Method (3D CAM) twice daily (8:00-10:00 and 18:00-20:00).

    Measured: Up to the 5th day after surgery

  6. 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

  7. Length of stay in hospital after surgery

    Length of stay in hospital after surgery

    Measured: Up to 30 days after surgery

  8. Duration requiring analgesics within 30 days after surgery

    Duration requiring analgesics within 30 days after surgery

    Measured: Up to 30 days after surgery

  9. Incidence of postoperative complications within 30 days

    Postoperative complications are defined as new-onset medical conditions that were deemed harmful and required therapeutic intervention (i.e., grade II or higher on the Clavien-Dindo classification)

    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 posted10 Mar 2021
  2. Study start9 Apr 2021
  3. Primary completion7 Sep 2022
  4. Study completion7 Oct 2022

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
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04791059
Sponsor's protocol ID
2020-465
Status last verified
Dec 2022
First submitted
8 Mar 2021
Last updated
13 Dec 2022
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
  • 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
  • Seki H, Ideno S, Ishihara T, Watanabe K, Matsumoto M, Morisaki H. Postoperative pain management in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis: a narrative review. Scoliosis Spinal Disord. 2018 Sep 12;13:17. doi: 10.1186/s13013-018-0165-z. eCollection 2018.

    PubMed 30214945
  • Nielsen RV. Adjuvant analgesics for spine surgery. Dan Med J. 2018 Mar;65(3):B5468.

    PubMed 29510816
  • 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
  • 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. Focus (Am Psychiatr Publ). 2019 Jan;17(1):55-65. doi: 10.1176/appi.focus.17105. Epub 2019 Jan 7.

    PubMed 32015715
  • 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
  • Persson 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 11936706
  • Stone LS, MacMillan LB, Kitto KF, Limbird LE, Wilcox GL. The alpha2a adrenergic receptor subtype mediates spinal analgesia evoked by alpha2 agonists and is necessary for spinal adrenergic-opioid synergy. J Neurosci. 1997 Sep 15;17(18):7157-65. doi: 10.1523/JNEUROSCI.17-18-07157.1997.

    PubMed 9278550
  • Peng K, Zhang J, Meng XW, Liu HY, Ji FH. Optimization of Postoperative Intravenous Patient-Controlled Analgesia with Opioid-Dexmedetomidine Combinations: An Updated Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials. Pain Physician. 2017 Nov;20(7):569-596.

    PubMed 29149140
  • Wu XH, Cui F, Zhang C, Meng ZT, Wang DX, Ma J, Wang GF, Zhu SN, Ma D. Low-dose Dexmedetomidine Improves Sleep Quality Pattern in Elderly Patients after Noncardiac Surgery in the Intensive Care Unit: A Pilot Randomized Controlled Trial. Anesthesiology. 2016 Nov;125(5):979-991. doi: 10.1097/ALN.0000000000001325.

    PubMed 27571256
  • Gao Y, Deng X, Yuan H, Leng Y, Zhang T, Xu X, Tian S, Fang J, Ouyang W, Wu X. Patient-controlled Intravenous Analgesia With Combination of Dexmedetomidine and Sufentanil on Patients After Abdominal Operation: A Prospective, Randomized, Controlled, Blinded, Multicenter Clinical Study. Clin J Pain. 2018 Feb;34(2):155-161. doi: 10.1097/AJP.0000000000000527.

    PubMed 28654556
  • Bornemann-Cimenti H, Wejbora M, Michaeli K, Edler A, Sandner-Kiesling A. The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial. Minerva Anestesiol. 2016 Oct;82(10):1069-1076. Epub 2016 Jun 21.

    PubMed 27327855

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing S-ketamine, 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 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 13 Dec 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.

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?

Percent of patients with moderate to severe pain within 72 hours (time frame: Up to 72 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 NCT04791059, which also lists 20 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 Dec 2022.

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