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Acute PainPhase 4NCT02767882

Dexamethasone in Pain Control After Total Knee Replacement

A Phase 4 study testing Dexamethasone and Saline in people with Acute Pain, run by The University of Hong Kong at 1 site in Hong Kong.

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

The primary aims of total knee replacement are improvement in functional activities and reduce pain due to degenerated knee joints. However, there are around 20-30% of patients would develop significant pain problem despite uncomplicated total knee replacement. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Acute Pain
What is being tested?
Dexamethasone and Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
138 participants
Where
1 siteHong Kong
Study dates
1 May 2016to 31 Dec 2020
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

  • ASA I-III
  • Age 18-80 years old
  • Scheduled for elective primary unilateral total knee replacement
  • Chinese patients
  • Able to speak and understand Cantonese
  • Able to provide informed oral and written consent

Who cannot join

  • Revision total knee replacement
  • Single stage bilateral total knee replacement
  • Known allergy to opioids, local anaesthetic drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDS) including COX-2 inhibitors
  • History of chronic pain other than chronic knee pain
  • History of insulin dependent diabetic mellitus, but not diabetic mellitus on oral hyperglycaemic agents
  • History of hepatitis B or C carrier
Show all 22Show fewer
  • History of peptic ulcer
  • Hx of tuberculosis
  • History of immunosuppression
  • Daily use of glucocorticoids
  • Daily use of strong opioids (morphine, fentanyl, hydromorphone, ketobemidone, methadone, nicomorphine, oxycodone, or meperidine)
  • History of severe heart disease (NYHA 2)
  • Alcohol or drug abuse
  • Impaired renal function, defined as preoperative serum creatinine level over 120micromol/L
  • Pre-existing neurological or muscular disorders
  • Psychiatric illness or neurologic or psychiatric diseases potentially influencing pain perception
  • Impaired or retarded mental state
  • Difficulties in using patient controlled analgesia (PCA)
  • Pregnancy
  • Local infection
  • On immunosuppresants
  • Patient refusal

Trial locations and contacts

1 site in 1 country.

Hong Kong1 site
  • Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

About this study

Official title: Effects of Preoperative Dexamethasone in Post-operative Pain Control After Total Knee Replacement

The primary aims of total knee replacement are improvement in functional activities and reduce pain due to degenerated knee joints. However, there are around 20-30% of patients would develop significant pain problem despite uncomplicated total knee replacement. It accounts for major post-operative problems and burdens.

Dexamethasone is glucocorticoid which is associated with anti-inflammatory response. It is well known to have prophylaxis effect for post-operative nausea and vomiting. Perioperative single dose of systemic dexamethasone have shown to be useful for reduction in pain and cumulative opioid consumption. Meta-analysis from De Oliveira et al supports that dexamethasone (up to 0.2 mg/kg) is a safe and effective multimodal pain strategy after surgical procedures. However, this dose recommendation is not surgery specific. It is essential to have more RCTs evaluating the optimal dose of steroid for pain management after hip and knee surgery.

Read the detailed description

Patients will be approached at the preadmission clinic or in the general ward before operation. The analgesic methods will be explained and s/he will be recruited into the study if s/he agrees. There are standardized preoperative, intraoperative and postoperative analgesic regimes for patients undergoing total knee replacement.

For preoperative analgesic regime, pregabalin 50mg are given the night before operation. Same analgesic regime is used on the day before operation. For intraoperative regime, standardized intraarticular local anaesthetic infiltration is used. For postoperative analgesic regime, PCA using morphine is used. In addition to PCA using morphine, standardized analgesic regime is used -- regular pregabalin 50mg nocte, paracetmal 1g QID, Celebrex 200mg BD will be given for 5 days.

Patients will be randomized into one of three groups. Patients in the first group (D1) will receive standardized oral analgesic regime pre-operatively, intraoperatively and postoperatively. In addition to the above, they will be given preoperative intravenous 8mg dexamethasone. Patients in the second (D2) group will be given preoperative intravenous 16mg dexamethasone, in addition to same pre-operative, intraoperative and post-operative analgesic regimes. Patients in the third (C) group will be given preoperative intravenous 4ml 0.9% saline, in addition to same pre-operative, intraoperative and post-operative analgesic regimes.

Preoperative Care Assessment will be done at the preadmission clinic or at the general ward. Pre-operative pregabalin will be given before operation and on the day before operation. Fasting will start six hours before operation.

Range of movement of the operating knee, quadriceps function, pain scores of the affecting knee will be assessed on day before operation.

Pre-operative inflammatory marker (e.g. CRP, ESR, tumour necrosis factor α, interleukin IL-6) and H'stix will be taken on day of admission.

Anaesthetic and intraoperative care

All patients will be anaesthetized according to the following protocol:

On arrival to the operation theatre, a 18 or 16 gauge intravenous cannula will be inserted. Standard monitoring with pulse oximeter, non-invasive blood pressure, and three lead electrocardiogram will be applied prior to induction. Non-invasive blood pressure will be checked at least every 5 minutes throughout the operation.

Patients will be provided with spinal anaesthesia for the operation with 2.4 ml 0.5% heavy Marcaine will be administrated into spinal space after position confirmed with spinal needle. No intrathecal opioid will be given during the procedure. Patient will be sedated with TCI propofol (0.3 -1 ug/ml) throughout the whole total knee replacement after successful spinal anaesthesia.

Intravenous antibiotic will be given before skin incision. Hypotension will be managed with intravenous phenylephrine or ephedrine at the discretion of the anaesthesiologist. Intra-operative fluid 8-10ml/kg/hr will be infused as maintenance. Also intravenous bolus of fluid will be given for replacement of blood loss. Infusion fluid warmer and thermal blanket will be used with the aim of keeping a core temperature of 35.5-37.5 degrees Celsius.

Local anaesthetic infiltration of 40ml 0.75% ropivacaine, 0.5ml 1:200,000 adrenaline, 30mg ketorolac in 60ml normal saline will be administrated by orthopaedic surgeons after implant insertion and wound closure.

Patients will subsequently be transferred to the post anaesthetic care unit (PACU) for monitoring for at least 1 hour. H'stix and H'cue will be checked 2 hours and 4 hours after preoperative injection of dexamethasone.

Analgesic modalities and pain assessment

Procedures for the all analgesic modalities are described below:

Group D1 Patients from group D will be given a bolus injection of 2 ml saline with 2 ml dexamethasone (4mg/ml) before skin incision.

Group D2 4ml bolus injection of dexamethasone (4mg/ml) will be given intravenously prior to incision.

Group C 4ml bolus injection of 0.9% saline will be given intravenously prior to incision.

For all groups In the recovery room after surgery, boluses of 2mg intravenous morphine will be given every 5 minutes until numerical rating pain score (NRS) is less than 4/10. A PCA machine will then be connected. The machine will be configured to give 1mg of morphine at a time and the lockout duration will be set to 5 minutes. No background infusion will be given and the maximum dose limit will be 0.1mg/kg per hour of morphine sulphate.

Intramuscular morphine sulphate at a dose of 0.1mg/kg will be prescribed every 4 hours if necessary for breakthrough beginning from postoperative day 0. Intravenous 4mg ondansetron is used every 4 hours if necessary if there is any nausea or vomiting.

On postoperative day 0, patient will resume oral diet if not contraindicated. Oral paracetamol and COX-2 inhibitor will be given for 5 days. Oral pregabalin will be given for 7 days.

While on PCA morphine, the patient's respiratory rate, SpO2 and sedation score will be monitored every hour. Heart rate and blood pressure will be checked every 4 hours. NRS pain scores at rest, during knee movement, during sleep, cumulative PCA morphine doses, and number of PCA demands/goods delivered, and side effects (nausea, vomiting, dizziness) will be recorded every 4 hours. Patients will be assessed by pain team everyday.

Patients will be on PCA morphine for at least 2 days. If NRS pain scores during knee movement on postoperative day 2 is less than 4/10 or clinically low morphine consumption, PCA morphine will be stopped. PCA morphine will be continued if NRS is equal or greater than 4, or if the patient remains on a high PCA consumption.

After PCA morphine has stopped, NRS pain scores at rest and during knee movement, as well as the dose and frequency of rescue analgesia used will be charted once a day until discharge.

Surgical technique/Prosthesis The surgery will be performed by the same surgical team with standardized surgical technique. All the patients will have posterior stabilized knee prosthesis. Tranexamic acid will be given according to our protocol. Standardized regimen and technique of local infiltration of analgesic at the end of the surgery will be given as part of the multi-modal pain control protocol

Postoperative care and assessment Day zero mobilization or early mobilization with PT and OT rehabilitation is encouraged after operation. Fluid diet will be allowed on postoperative day 0.

The surgical team will assess for occurrences of postoperative surgical complications, suitability for discharge (good pain control, ambulation, normal bowel function, and ability to eat properly without vomiting. Urinary retention will be documented as well.

Range of movement of the operating knee and other rehabilitation parameters will be assessment by allied health staffs from Day 0 till day of discharge.

Side effects of steroid are documented e.g. gastrointestinal bleeding, hyperglycaemia, wound infection (Southampton wound assessment scale), or other systemic infections are documented.

Glucose level will be measured in 7am and 5pm on Day 1 and Day 2. Insulin will be used to keep glucose <15 mmol/dl. Blood investigations will also be performed. Inflammatory marker e.g. ESR, CRF, tumour necrosis factor α, interleukin IL-6 will be taken on Day 0, Day 1 and Day 2. Haemoglobin level and the need of transfusion will be documented.

Conditions
Acute Pain
Being tested
Dexamethasone, Saline
Medical subject headings
Acute Pain

What participants receive

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

  • DexamethasoneDrug

    Bolus injection of different dose of dexamethasone will be given intravenously prior to incision.

  • SalineDrug

    Bolus injection of 4ml 0.9% saline will be given intravenously prior to incision.

Study groups in NCT02767882
Study groupRoleWhat they receive
Group D1Active comparatorPatients from group D will be given a bolus injection of 2 ml saline with 2 ml dexamethasone (4mg/ml) before skin incision.
Receives: Drug: Dexamethasone
Group D2Experimental4ml bolus injection of dexamethasone (4mg/ml) will be given intravenously prior to incision.
Receives: Drug: Dexamethasone
Group CPlacebo comparator4ml bolus injection of 0.9% saline will be given intravenously prior to incision
Receives: Drug: Saline

What is being measured

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

  1. pain score

    Pain will be measured using numerical rating scale from 0 to 10 with 0 is no pain and 10 is the worst pain

    Measured: at postoperative day 1

Secondary outcomes (1)
  1. quality of recovery

    quality of recovery will be measured using Quality of Recovery Questionnaire

    Measured: at postoperative day 1

Timeline

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

  1. First posted10 May 2016 (estimated)
  2. Study start1 May 2016
  3. Primary completion31 Jan 2019
  4. Study completion31 Dec 2020

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
Double blind
Who is masked
Participant, Investigator
Enrolment
138 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02767882
Sponsor's protocol ID
UW16-201
Status last verified
May 2022
First submitted
6 May 2016
Last updated
23 May 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Chan TCW, Cheung CW, Wong SSC, Chung AYF, Irwin MG, Chan PK, Fu H, Yan CH, Chiu KY. Preoperative dexamethasone for pain relief after total knee arthroplasty: A randomised controlled trial. Eur J Anaesthesiol. 2020 Dec;37(12):1157-1167. doi: 10.1097/EJA.0000000000001372.

    PubMed 33105245

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dexamethasone and Saline in people with Acute Pain, run by The University of Hong Kong at 1 site in Hong Kong.

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 6 inclusion and 22 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 23 May 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 Hong Kong. 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?

pain score (time frame: at postoperative day 1). 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 NCT02767882, 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 23 May 2022.

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Clinical Trial NCT02767882 | AzTrials