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.
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.
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).
- Conditions
- Osteoarthritis, Knee
- 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 group | Role | What they receive |
|---|---|---|
| Methylprednisolone Group | Experimental | The 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 Group | Placebo comparator | The 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.
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)
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
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
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
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
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
Time to achieve independent frame walking
in terms of days
Measured: upon discharge usually around post operative day 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
Patient-controlled analgesia consumption
Total morphine use in patient-controlled analgesia
Measured: 48 hours after surgery
Rescue analgesics consumption
amount of rescue analgesics (DF118) needed
Measured: upon discharge usually around post operative day 7
Knee circumference of the operated knee
measured at most superior border of patella in cm
Measured: 48 hours after surgery
C-reactive Protein
blood taking for C-reactive protein
Measured: day 1 after surgery
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.
- First posted17 Mar 2017
- Study start1 Jun 2017
- Primary completion1 Jun 2019
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Queen Elizabeth Hospital, Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cheng Lok Yiu, Queen Elizabeth Hospital, Hong Kong
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
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-operative Intravenous Steroid in Unilateral Primary Total Knee Replacement for Pain Relief and Recovery: A Double-Blind Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03082092
- Acronym / sponsor ID
- PISTKR
- Conditions
- Osteoarthritis, Knee
- Keywords
- Knee, Pain, Recovery, Steroid, Replacement, Arthroplasty
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Queen Elizabeth Hospital, Hong KongUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 1 Jun 2019 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 17 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- single-centre, double-blind, placebo-controlled randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Methylprednisolone Group | Experimental | Drug: Methylprednisolone Sodium SuccinateThe intervention group will receive a single dose intravenous 125mg methylprednisolone diluted in 2.1ml of diluent on induction of total knee replacement. |
| Placebo Group | Placebo comparator | Drug: PlacebosThe 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 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Elective unilateral total knee replacement for primary osteoarthritis of knee
- ASA (American Society of Anesthesiologists) grading 1 or 2
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylprednisolone Sodium Succinatesingle intravenous dose of 125mg methylprednisolone diluted in 2.1ml of diluent given on induction of total knee replacement | Drug | Methylprednisolone Group |
| Placebos0.9% intravenous saline (2.1ml) intravenously on induction of total knee replacement | Drug | Placebo Group |
Primary outcome
Pain from operated knee using 100mm visual analogue scale
Time frame: 24 hours after surgery
during walking 5 metres with frame, using 100mm visual analogue scale
12 secondary outcomes
Pain from operated knee (other than primary outcome) using 100mm visual analogue scale
Time frame: 24 hours after surgery
Pain from operated knee using 100mm visual analogue scale
Time frame: 30 hours after surgery
Pain from operated knee using 100mm visual analogue scale
Time frame: 48 hours after surgery
Pain from operated knee using 100mm visual analogue scale
Time frame: upon discharge usually around post operative day 7
Range of movement from operated knee
Time frame: 24, 30, 48 hours after surgery, upon discharge usually around post operative day 7
Time to achieve independent frame walking
Time frame: upon discharge usually around post operative day 7
Length of stay
Time frame: upon discharge usually around post operative day 7
Patient-controlled analgesia consumption
Time frame: 48 hours after surgery
Rescue analgesics consumption
Time frame: upon discharge usually around post operative day 7
Knee circumference of the operated knee
Time frame: 48 hours after surgery
C-reactive Protein
Time frame: day 1 after surgery
Sleep quality using 0-100 visual analogue scale
Time frame: day 1 after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- Derived from this study: PubMed 31222540Cheng 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
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.