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Osteoarthritis, KneePhase 4NCT03082092

Pre-operative Intravenous Steroid in Total Knee Replacement for Pain Relief and Recovery

A Phase 4 study testing Methylprednisolone Sodium Succinate in people with Osteoarthritis, Knee, run by Queen Elizabeth Hospital, 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

Osteoarthritis of the knee is a common and important condition in our society. Despite various anesthetic methods and pain medications, pain after operation still remains as a challenge. Steroids plays a role in decreasing the inflammatory reaction and stress response from surgery. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Osteoarthritis, Knee
What is being tested?
Methylprednisolone Sodium Succinate
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteHong Kong
Study dates
1 Jun 2017to 1 Jun 2019
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

  • Elective unilateral total knee replacement for primary osteoarthritis of knee
  • ASA (American Society of Anesthesiologists) grading 1 or 2

Who cannot join

  • Rheumatoid arthritis or seronegative arthritis
  • Allergy to any medications used in the standard protocol (Methylprednisolone, adrenaline, ropivacaine, ketorolac, bupivacaine, ketorolac, pepcidine, transamin, gabapentin, voltaren, panadol, DF118)
  • Chronic opioid use
  • Substance dependence
  • Patients attending chronic pain clinic
  • Psychiatric or neurological condition that may influence pain perception or reporting
Show all 10Show fewer
  • Chronic illness that preclude the use of the medications in the standard protocol
  • Hepatitis B carrier or Elevated bilirubin or ALT
  • Active peptic ulcer disease
  • Uncontrolled diabetic patients with HbA1c >7% in recent 3 months

Trial locations and contacts

1 site in 1 country.

Hong Kong1 site
  • Queen Elizabeth Hospital

    Hong Kong

Other trials in Hong Kong

About this study

Official title: Pre-operative Intravenous Steroid in Unilateral Primary Total Knee Replacement for Pain Relief and Recovery: A Double-Blind Randomized Controlled Trial

Osteoarthritis of the knee is a common and important condition in our society. Despite various anesthetic methods and pain medications, pain after operation still remains as a challenge.

Steroids plays a role in decreasing the inflammatory reaction and stress response from surgery.

Read more

This study is to evaluate the use of an additional steroid injection, on top of usual pain killers and anesthesia, on the effect of pain control and recovery after total knee replacement.

50 subjects will be recruited, half of them will be randomized to receive a single dose of steroid injection before operation while the other half will receive a placebo. All the doctors, patients and physiotherapists are not aware of the allocation. Apart from the steroid or placebo injection, all the other treatment (eg: surgery, medications, rehabilitation protocol etc) will be the same. Doctors and physiotherapists will assess the subjects at 24, 30, 48 hours after surgery and upon discharge for their pain relief and recovery. Any complications will also be documented.

Read the detailed description

Osteoarthritis of the knee is a common and important disease in the population. As a joint replacement centre, around 600 total knee replacements were performed in Queen Elizabeth Hospital and Buddhist Hospital per year. Despite multiple anesthetic methods and analgesics protocols, post-operative pain remains a significant problem.

Perioperative use of steroids has been shown to reduce postoperative nausea and vomiting. In both orthopaedic and non-orthopaedic operations, a single high dose of pre-operative steroid was also found to be effective in reducing early postoperative pain.

The hypothesis is that steroids help reduce post-operative inflammation and surgical stress response. Inflammatory markers such as IL-6 and C-reactive protein showed significant reduction after administration of perioperative steroids.

In a Denmark randomized-controlled trial published in 2010, the authors found that a single high-dose of methylprednisolone significantly reduce post-operative pain upto 48 hours in patients undergoing unilateral primary total knee replacement. Another randomized-controlled trial conducted in Korea in 2013 also showed significant pain control with less opioid consumption 6-24 hours after total knee replacement using dexamethasone. A group of United States researchers demonstrated that 3 doses of perioperative low dose hydrocortisone could also reduce post-bilateral total knee replacement pain at 24 hours with significant greater range of motion in a randomized-controlled trial published in 2012. However, there is no data on the effect of perioperative steroid use in Chinese population receiving total knee arthroplasty.

Upon induction, the intervention group will receive 125mg methylprednisolone diluted in 2.1ml of diluent intravenously. The placebo group will receive 2.1ml of 0.9% intravenous saline, which is transparent and has no difference in appearance to methylprednisolone.

All subjects will undergo total knee replacement using same implant (Zimmer NexGen LPS Flex) by same surgeons. All operations will be done under spinal anesthesia injecting 1.8-2.5ml 0.5% Bupivacaine into L3/4 or L4/5 disc space without fentanyl or other analgesics. Pre-operative, perioperative and postoperative analgesic regimen will be standardised.

Subjects will be assessed at 24, 30, 48 hours after surgery and upon discharge by physiotherapists. During each assessment, pain from operated knee will be assessed with 100mm visual analogue scale with patients performing different tasks, i.e.: at rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, frame walking for 5m. Range of movement will also be documented in each assessment. Time to achieve independent frame walking and length of stay will be recorded in terms of days.

Analgesic consumption will be calculated with reference to the total amount of morphine administered through patient-controlled analgesia in the first 48 hours and the total dosage of rescue analgesia (DF118) required.

To assess the severity of inflammation, knee circumference (measured at the most superior border of patella in cm) will be measured before operation and 48 hours after operation. Biochemically, blood will be taken for C-reactive protein (CRP) in day 1 after surgery and compared with pre-operative CRP. Renal function and blood sugar will also be closely monitored to detect any hypokalaemia or hyperglycaemia. Subjects will also be asked to rate the sleep quality using a 100mm visual analogue scale (0 = worst sleep, 100 = best sleep).

Being tested
Methylprednisolone Sodium Succinate, Placebos
Keywords
Knee, Pain, Recovery, Steroid, Replacement, Arthroplasty
Medical subject headings
Osteoarthritis, Knee, Pain

What participants receive

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

  • Methylprednisolone Sodium SuccinateDrug

    single intravenous dose of 125mg methylprednisolone diluted in 2.1ml of diluent given on induction of total knee replacement

  • PlacebosDrug

    0.9% intravenous saline (2.1ml) intravenously on induction of total knee replacement

Study groups in NCT03082092
Study groupRoleWhat they receive
Methylprednisolone GroupExperimentalThe intervention group will receive a single dose intravenous 125mg methylprednisolone diluted in 2.1ml of diluent on induction of total knee replacement.
Receives: Drug: Methylprednisolone Sodium Succinate
Placebo GroupPlacebo comparatorThe placebo group will receive a single dose intravenous 2.1ml of 0.9% IV saline, which is transparent and has no difference in appearance to methylprednisolone, on induction of total knee replacement
Receives: Drug: Placebos

What is being measured

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

  1. Pain from operated knee using 100mm visual analogue scale

    during walking 5 metres with frame, using 100mm visual analogue scale

    Measured: 24 hours after surgery

Secondary outcomes (12)
  1. Pain from operated knee (other than primary outcome) using 100mm visual analogue scale

    during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, using 100mm visual analogue scale

    Measured: 24 hours after surgery

  2. Pain from operated knee using 100mm visual analogue scale

    during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, walking 5 metres with frame, using 100mm visual analogue scale

    Measured: 30 hours after surgery

  3. Pain from operated knee using 100mm visual analogue scale

    during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, walking 5 metres with frame, using 100mm visual analogue scale

    Measured: 48 hours after surgery

  4. Pain from operated knee using 100mm visual analogue scale

    during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, walking 5 metres with frame, using 100mm visual analogue scale

    Measured: upon discharge usually around post operative day 7

  5. Range of movement from operated knee

    Maximal knee flexion and maximal knee extension

    Measured: 24, 30, 48 hours after surgery, upon discharge usually around post operative day 7

  6. Time to achieve independent frame walking

    in terms of days

    Measured: upon discharge usually around post operative day 7

  7. Length of stay

    from day of admission to day of discharge, in terms of days

    Measured: upon discharge usually around post operative day 7

  8. Patient-controlled analgesia consumption

    Total morphine use in patient-controlled analgesia

    Measured: 48 hours after surgery

  9. Rescue analgesics consumption

    amount of rescue analgesics (DF118) needed

    Measured: upon discharge usually around post operative day 7

  10. Knee circumference of the operated knee

    measured at most superior border of patella in cm

    Measured: 48 hours after surgery

  11. C-reactive Protein

    blood taking for C-reactive protein

    Measured: day 1 after surgery

  12. Sleep quality using 0-100 visual analogue scale

    0-100 visual analogue scale, 0=worst sleep, 100= best sleep

    Measured: day 1 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 posted17 Mar 2017
  2. Study start1 Jun 2017
  3. Primary completion1 Jun 2019
  4. Study completion1 Jun 2019

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
Model description
single-centre, double-blind, placebo-controlled randomized controlled trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03082092
Sponsor's protocol ID
PISTKR
Status last verified
Aug 2019
First submitted
25 Feb 2017
Last updated
4 Sep 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cheng BLY, So EHK, Hui GKM, Yung BPK, Tsui ASK, Wang OKF, Poon MWY, Chan ACM, Wong SHS, Li W, Yip PSC. Pre-operative intravenous steroid improves pain and joint mobility after total knee arthroplasty in Chinese population: a double-blind randomized controlled trial. Eur J Orthop Surg Traumatol. 2019 Oct;29(7):1473-1479. doi: 10.1007/s00590-019-02469-5. Epub 2019 Jun 20.

    PubMed 31222540

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Methylprednisolone Sodium Succinate in people with Osteoarthritis, Knee, run by Queen Elizabeth Hospital, 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 2 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 4 Sep 2019. 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 from operated knee using 100mm visual analogue scale (time frame: 24 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 NCT03082092, 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 4 Sep 2019.

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