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Postoperative PainPhase 4NCT02085577

The Effect of Intraoperative Ketamine on Opioid Consumption and Pain After Spine Surgery in Opioid-dependent Patients

A Phase 4 study testing (S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml, Isotonic sodium chloride 0.9 percent and Paracetamol 1 g in people with Postoperative Pain and Chronic Pain, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

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

Patients with a daily use of opioids may develop higher postoperative pain levels, often need high doses of morphine and therefore their pain may be difficult to treat. A low dose of an old anesthetic drug, ketamine, administered during surgery can possibly reduce pain and morphine consumption in these patients. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Postoperative Pain, Chronic Pain, Analgesics
What is being tested?
(S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml, Isotonic sodium chloride 0.9 percent and Paracetamol 1 g
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
147 participants
Where
1 siteDenmark
Study dates
May 2014to 1 Nov 2016
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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients undergoing lumbar spinal fusion surgery in general anesthesia.
  • Daily use of opioids for a minimum of 6 weeks preoperatively (morphine, ketobemidone, oxycodone, fentanyl, tramadol and/or buprenorphine).
  • Back pain for a minimum of 3 months preoperatively.
  • Age > 18 years and < 85 years.
  • ASA 1-3.
  • BMI > 18 and < 40.
  • Fertile women need to have a negative urine HCG pregnancy test.
  • Patients who have given their written informed consent to participate in the study after understanding the content and limitations of the study

Who cannot join

  • Participation in another concomitant drug trial.
  • Patients who do not understand or speak Danish.
  • Allergy to the drugs used in the trial.
  • Abuse of drugs - as assessed by the investigator.
  • Daily methadone use.
  • Increased intraocular pressure - assessed from the patients chart.
  • Uncontrolled hypertension - assessed from the patients chart.
  • Previous and current psychotic episodes - assessed from the patients chart

Trial locations and contacts

1 site in 1 country.

Denmark1 site
  • Department of Anaesthesiology, Glostrup Hospital

    Glostrup Municipality, 2600

Other trials in Denmark

About this study

Patients with a daily use of opioids may develop higher postoperative pain levels, often need high doses of morphine and therefore their pain may be difficult to treat. A low dose of an old anesthetic drug, ketamine, administered during surgery can possibly reduce pain and morphine consumption in these patients. Our purpose is to investigate the effect of low dose ketamine on morphine consumption and pain after spine surgery in patients with a daily use of opioids. Our hypothesis is that low dose ketamine can reduce morphine consumption, pain and side-effects after spine surgery.

Read the detailed description

Opioid-dependent patients can develop hyperalgesia and often have a high opioid consumption postoperatively due to opioid tolerance. Intraoperative ketamine in subanesthetic doses can possibly reduce hyperalgesia and reduce opioid-tolerance in these patients. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that works by blocking the NMDA receptors in the central and peripheral nerve system. It can be used for general anesthesia but the drug also has other properties including lowering of central excitability and reducing postoperative opioid tolerance by modeling the opioid receptors. Further more it can possibly reduce chronic pain by blocking wind-up effect when blocking the NMDA receptors.

Our purpose is to investigate the effect of intraoperative ketamine on opioid consumption and pain after spine surgery in opioid-dependent patients. Our hypothesis is that ketamine can reduce opioid consumption and reduce postoperative pain and side effects compared to placebo.

Being tested
(S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml, Isotonic sodium chloride 0.9 percent, Paracetamol 1 g, Morphine Sulphate 1 mg/ml, Ondansetron 2 mg/ml
Keywords
Morphine consumption, Postoperative pain, Ketamine, Side effects, Spine surgery, Chronic pain
Medical subject headings
Pain, Postoperative, Chronic Pain

What participants receive

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

  • (S)-(+)-Ketamine Hydrochloride Solution 25 mg/mlDrug

    Also called Ketamine

    Ketamine (25 mg/ml) bolus 0.5 mg/kg administered immediately after induction of anesthesia, followed by infusion ketamine 0,25 mg/kg/hour that is terminated when the last suture to the skin has been performed.

  • Isotonic sodium chloride 0.9 percentDrug

    Also called Isotonic saline

    Isotonic sodium chloride 0.9 percent 0.02 ml/kg administered immediately after induction of anesthesia, followed by infusion isotonic sodium chloride 0.01 ml/kg/hour that is terminated when the last suture to the skin has been performed.

  • Paracetamol 1 gDrug

    Also called Paracetamol

    Paracetamol 1 g orally 1 hour preoperatively and every 6 hours after extubation time during the first 24 hours.

  • Morphine Sulphate 1 mg/mlDrug

    Also called Morphine

    Morphine Sulphate 1 mg/ml administered as patient-controlled analgesia (PCA, bolus 2.5 mg, lockout 5 minutes) 0-24 hours postoperatively

  • Morphine Sulphate 1 mg/mlDrug

    Also called Morphine

    Morphine Sulphate 1 mg/ml, bolus 2.5 mg administered by the PACU nurse on request of the patient for the first hour postoperatively.

  • Ondansetron 2 mg/mlDrug

    Also called Zofran

    Ondansetron 2 mg/ml 4 mg iv in case of moderate to severe nausea, supplemented by Ondansetron 1 mg iv if needed

  • Usual daily opioidsDrug

    Also called Morphine

    The patients usual daily opioid consumption are administered during the study period

  • Morphine Sulphate 1 mg/mlDrug

    Also called Morphine

    Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.

  • Sufentanil 5 microgram/mlDrug

    Also called Sufentanil

    Sufentanil 5 microgram/ml, bolus 5 micrograms administered by the anaesthetic nurse in the operating room if the patient is in pain upon awakening.

Study groups in NCT02085577
Study groupRoleWhat they receive
KetamineExperimental* (S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml bolus 0.5 mg/kg administered immediately after induction of anesthesia, followed by infusion ketamine 0,25 mg/kg/h terminated at last suture to the skin. * Morphine. Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 min before expected awakening. * Escape sufentanil. Sufentanil 5 microgram/ml, bolus 5 micrograms administered by the anaesthetic nurse in the operating room if the patient is in pain upon awakening. * Morphine. PCA-morphine, bolus 2.5 mg, lock-out-time 5 min. Concentration : Morphine sulphate 1 mg/ml. * Escape morphine. Morphine Sulphate 1 mg/ml, bolus 2.5 mg administered by the PACU nurse on request of the patient for the first hour postoperatively. * Ondansetron 2 mg/ml, 4 mg iv in case of moderate to severe nausea, supplemented by 1 mg iv if needed * Paracetamol 1 g orally 1 h preoperatively and every 6 h after extubation time during the first 24 h. * The patients usual daily opioids
Receives: Drug: (S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml; Drug: Paracetamol 1 g; Drug: Morphine Sulphate 1 mg/ml; Drug: Ondansetron 2 mg/ml; Drug: Usual daily opioids; Drug: Sufentanil 5 microgram/ml
PlaceboPlacebo comparator* Isotonic sodium chloride 0.9 percent 0.02 ml/kg administered immediately after induction of anesthesia, followed by infusion isotonic sodium chloride 0.01 ml/kg/h terminated at last suture to the skin. * Morphine. Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 min before expected awakening. * Escape sufentanil. Sufentanil 5 microgram/ml, bolus 5 micrograms administered by the anaesthetic nurse in the operating room if the patient is in pain upon awakening. * Morphine. PCA-morphine, bolus 2.5 mg, lock-out-time 5 min. Concentration : Morphine sulphate 1 mg/ml. * Escape morphine. Morphine Sulphate 1 mg/ml, bolus 2.5 mg administered by the PACU nurse on request of the patient for the first hour postoperatively. * Ondansetron 2 mg/ml, 4 mg iv in case of moderate to severe nausea, supplemented by 1 mg iv if needed * Paracetamol 1 g orally 1 h preoperatively and every 6 h after extubation time during the first 24 h. * The patients usual daily opioids
Receives: Drug: Isotonic sodium chloride 0.9 percent; Drug: Paracetamol 1 g; Drug: Morphine Sulphate 1 mg/ml; Drug: Ondansetron 2 mg/ml; Drug: Usual daily opioids; Drug: Sufentanil 5 microgram/ml

What is being measured

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

  1. Morphine consumption

    Total intravenous morphine consumption, other than the patients usual opioid use, 0- 24 hours postoperatively, administered as patient-controlled analgesia ((PCA), bolus 2.5 mg, lockout 5 minutes)

    Measured: 0-24 hours postoperatively

Secondary outcomes (9)
  1. Pain during mobilization

    Pain score during active mobilization, measured on a visual analogue scale (VAS) (0-100 mm), defined as a standardized movement from recumbent position to sitting on the bedside at 2, 6, 12, 18 and 24 hours postoperatively, the worst pain from the movement is registered. The endpoint, VAS-mobilization, will be calculated as area under the curve (AUC) (2-24h) from these measurements.

    Measured: 2, 6, 12, 18 and 24 hours postoperatively

  2. Pain at rest

    Pain score at rest, measured on a visual analogue scale (VAS) (0-100 mm), at 2, 6, 12, 18 and 24 hours postoperatively. The endpoint, VAS-rest, will be calculated as area under the curve (AUC) (2-24h) from these measurements.

    Measured: 2, 6, 12, 18 & 24 hours postoperatively

  3. Nausea

    Level of nausea (none, mild, moderate, severe) (0-24h), measured at 2, 6, 12, 18 and 24 hours postoperatively.

    Measured: 2, 6, 12, 18 & 24 hours postoperatively

  4. Vomiting

    Number of vomiting episodes (0-24 hours), registered in the periods 0-2, 2-6, 6-12, 12-18, 18-24 hours postoperatively.

    Measured: 0-2, 2-6, 6-12, 12-18, 18-24 hours postoperatively

  5. Ondansetron

    Consumption of ondansetron (mg) during 0-24 hours postoperatively.

    Measured: 0-24 hours postoperatively

  6. Sedation

    Level of sedation (none, mild, moderate, severe) (0-24 h) registered at time 2, 6, 12, 18 and 24 hours postoperatively.

    Measured: 2, 6, 12, 18 & 24 hours postoperatively

  7. Hallucinations and nightmares

    Episodes of hallucinations and nightmares (yes/no) in the period 0-24 hours postoperatively.

    Measured: 0-24 hours postoperatively

  8. Chronic pain

    Level of chronic pain and daily use of opioids assessed by the validated questionnaires EQ50, OWESTRY and DN4 at 6 months postoperatively.

    Measured: 6 months postoperatively

  9. Chronic pain

    Level of chronic pain and daily use of opioids assessed by the validated questionnaires EQ50, OWESTRY and DN4 at 12 months postoperatively.

    Measured: 12 months postoperatively

Timeline

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

  1. First posted13 Mar 2014 (estimated)
  2. Study startMay 2014
  3. Primary completionOct 2015
  4. Study completion1 Nov 2016

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
147 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02085577
Sponsor's protocol ID
SM3-RS-2014
Other IDs
2014-000839-16, 2014
Status last verified
Apr 2017
First submitted
11 Mar 2014
Last updated
28 Apr 2017
Results posted
No
Data monitoring committee
No

Publications

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing (S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml, Isotonic sodium chloride 0.9 percent and Paracetamol 1 g in people with Postoperative Pain and Chronic Pain, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

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 8 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 28 Apr 2017. 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 Denmark. 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?

Morphine consumption (time frame: 0-24 hours postoperatively). 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 NCT02085577, which also lists 1 linked publication.

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 28 Apr 2017.

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