OsteoarthrosisPhase 3NCT02319343
Effect of Methylprednisolone on Quadriceps Muscle Function in Patients Undergoing Total Knee-arthroplasty
A Phase 3 study testing Methylprednisolone and Isotonic Sodium Chloride in people with Osteoarthrosis, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
This study evaluates the pathophysiological effects of a single dose Methylprednisolone administered prior to total knee-arthroplasty (TKA). The investigators examine the effect on thigh muscle function to evaluate the efficacy of Methylprednisolone on knee-extension strength at discharge after TKA. Read more about this study
- Who is it for?
- Ages 55 to 80 years
- Conditions the study is for
- Osteoarthrosis
- What is being tested?
- Methylprednisolone and Isotonic Sodium Chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2015to Apr 2016
- Phase
- Phase 3
- 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 55 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Osteoarthrosis
- Undergoing total unilateral knee-arthroplasty surgery
- Speak and understand Danish
- Have given informed consent
Who cannot join
- Revision, bilateral or uni chamber knee-arthroplasty surgery
- General anaesthesia
- Allergy or intolerance towards Methylprednisolone
- Local or systemic infection
- Permanent systemic treatment with steroids within 30 days preoperatively
- Insulin-dependent diabetes
Show all 11Show fewer
- Active treatment of ulcer within 3 months preoperatively
- Cancer disease
- Autoimmune disease incl. rheumatoid arthritis
- Pregnant or breast feeding women
- Menopause <1 year
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Preoperative Intravenous High Dose Methylprednisolone on Quadriceps Muscle Function in Patients Scheduled for Total Knee-arthroplasty
This study evaluates the pathophysiological effects of a single dose Methylprednisolone administered prior to total knee-arthroplasty (TKA). The investigators examine the effect on thigh muscle function to evaluate the efficacy of Methylprednisolone on knee-extension strength at discharge after TKA.
Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo.
The investigators hypothesize that the group receiving Methylprednisolone will experience smaller loss of knee-extension strength compared to the placebo-group, early after TKA.
Read the detailed description
The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects in postoperative pain, postoperative nausea and vomiting are well-documented.
Knee-arthroplasty surgery and the inflammatory stress response in general affect the potential of recovery. The quadriceps muscle strength is shown to be reduced significantly (80%) early after surgery. The mechanism is thought related to inhibitory reflexes and pain caused by surgical induced inflammation around the knee joint. The effect of glucocorticoids on the quadriceps muscle function after knee-arthroplasty surgery is unknown and calls for further investigation.
The study is to be considered as explorative.
The primary analysis of the primary outcome measure is a comparison of the changes in knee extension strength from baseline to 48 hours postoperatively between the two groups.
For calculation of sample size the average loss of strength from baseline (before surgery) to 48 hours after TKA-surgery being 0.8 Nm/kg body weight (SD=0.39, Holm et al. 2010), a risk of type I errors 5% and a risk of type II errors 20% (80% power) were used. The sample size is estimated to reveal a group difference in knee extension strength of minimum 40%.
The primary analysis is carried out on all included patients (intention-to-treat) with baseline values as covariate. Secondary exploratory per-protocol analysis might be performed. Missing outcomes will be analysed using multiple imputation due to expected strong time trends.
The secondary outcome measures; a group difference of 6 sec. (Timed Up \& Go) and 2 cm (knee circumference) are considered clinically relevant. The statistical power is based on the calculation outlined above using the same test prerequisites.
For further details please also view the European Clinical Trials Database (EudraCT) registration:
EudraCT nr.: 2014-003395-23
- Conditions
- Osteoarthrosis
- Being tested
- Methylprednisolone, Isotonic Sodium Chloride
- Keywords
- Glucocorticoid, Quadriceps muscle function, Knee arthroplasty, total
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Solu-Medrol
Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo)
Isotonic Sodium ChlorideDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Methylprednisolone | Active comparator | Preoperative single high dose of Solu-Medrol 125 mg iv. Receives: Drug: Methylprednisolone |
| Isotonic Sodium Chloride | Placebo comparator | Preoperative single dose of isotonic Sodium Chloride. Receives: Drug: Isotonic Sodium Chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in isometric knee extension strength measured as Nm/kg from baseline to 48 hours after surgery
Measured: two days after surgery
Secondary outcomes (4)
Change in Timed Up & Go (sec.) from baseline (before surgery) to 48 hours after surgery
Measured: two days after surgery
Change in knee circumference (cm) from baseline (before surgery) to 48 hours after surgery
Measured: two days after surgery
Change in pain intensity from baseline (before surgery) to 48 hours after surgery
Measured: two days after surgery
Change in concentration of C-reactive Protein from baseline (before surgery) to 48 hours after surgery
Measured: two days after suregry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for OsteoarthrosisStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- 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 3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Bispebjerg Hospital
- Responsible party
- Principal investigator, Viktoria Oline Lindberg-Larsen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Viktoria Lindberg-Larsen, MD, Principal investigator, Section for Surgical Pathophysiology, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02319343
- Sponsor's protocol ID
- HK_VL_08_2014
- Status last verified
- Apr 2016
- First submitted
- 8 Dec 2014
- Last updated
- 8 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Husted H. Fast-track hip and knee arthroplasty: clinical and organizational aspects. Acta Orthop Suppl. 2012 Oct;83(346):1-39. doi: 10.3109/17453674.2012.700593.
PubMed 23205862Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. No abstract available.
PubMed 23663938Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP, Reed MR. Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop. 2014 Feb;85(1):26-31. doi: 10.3109/17453674.2013.874925. Epub 2013 Dec 20.
PubMed 24359028Malviya A, Martin K, Harper I, Muller SD, Emmerson KP, Partington PF, Reed MR. Enhanced recovery program for hip and knee replacement reduces death rate. Acta Orthop. 2011 Oct;82(5):577-81. doi: 10.3109/17453674.2011.618911. Epub 2011 Sep 6.
PubMed 21895500Lunn TH, Kristensen BB, Andersen LO, Husted H, Otte KS, Gaarn-Larsen L, Kehlet H. Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial. Br J Anaesth. 2011 Feb;106(2):230-8. doi: 10.1093/bja/aeq333. Epub 2010 Dec 3.
PubMed 21131371Bandholm T, Kehlet H. Physiotherapy exercise after fast-track total hip and knee arthroplasty: time for reconsideration? Arch Phys Med Rehabil. 2012 Jul;93(7):1292-4. doi: 10.1016/j.apmr.2012.02.014. Epub 2012 Feb 27.
PubMed 22494947Geborek P, Mansson B, Wollheim FA, Moritz U. Intraarticular corticosteroid injection into rheumatoid arthritis knees improves extensor muscles strength. Rheumatol Int. 1990;9(6):265-70. doi: 10.1007/BF00541322.
PubMed 2315606Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms and treatment perspectives. Semin Arthritis Rheum. 2010 Dec;40(3):250-66. doi: 10.1016/j.semarthrit.2009.10.001. Epub 2009 Dec 2.
PubMed 19954822Holte K, Kehlet H. Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications. J Am Coll Surg. 2002 Nov;195(5):694-712. doi: 10.1016/s1072-7515(02)01491-6. No abstract available.
PubMed 12437261Holm B, Kristensen MT, Bencke J, Husted H, Kehlet H, Bandholm T. Loss of knee-extension strength is related to knee swelling after total knee arthroplasty. Arch Phys Med Rehabil. 2010 Nov;91(11):1770-6. doi: 10.1016/j.apmr.2010.07.229.
PubMed 21044725
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Preoperative Intravenous High Dose Methylprednisolone on Quadriceps Muscle Function in Patients Scheduled for Total Knee-arthroplasty
- ClinicalTrials.gov ID
- NCT02319343
- Acronym / sponsor ID
- HK_VL_08_2014
- Conditions
- Osteoarthrosis
- Keywords
- Glucocorticoid, Quadriceps muscle function, Knee arthroplasty, total
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Bispebjerg Hospital
- Study start
- Jan 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 18 Dec 2014 (estimated)
- 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.
This study evaluates the pathophysiological effects of a single dose Methylprednisolone administered prior to total knee-arthroplasty (TKA). The investigators examine the effect on thigh muscle function to evaluate the efficacy of Methylprednisolone on knee-extension strength at discharge after TKA.
Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo.
The investigators hypothesize that the group receiving Methylprednisolone will experience smaller loss of knee-extension strength compared to the placebo-group, early after TKA.
Detailed description
The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects in postoperative pain, postoperative nausea and vomiting are well-documented.
Knee-arthroplasty surgery and the inflammatory stress response in general affect the potential of recovery. The quadriceps muscle strength is shown to be reduced significantly (80%) early after surgery. The mechanism is thought related to inhibitory reflexes and pain caused by surgical induced inflammation around the knee joint. The effect of glucocorticoids on the quadriceps muscle function after knee-arthroplasty surgery is unknown and calls for further investigation.
The study is to be considered as explorative.
The primary analysis of the primary outcome measure is a comparison of the changes in knee extension strength from baseline to 48 hours postoperatively between the two groups.
For calculation of sample size the average loss of strength from baseline (before surgery) to 48 hours after TKA-surgery being 0.8 Nm/kg body weight (SD=0.39, Holm et al. 2010), a risk of type I errors 5% and a risk of type II errors 20% (80% power) were used. The sample size is estimated to reveal a group difference in knee extension strength of minimum 40%.
The primary analysis is carried out on all included patients (intention-to-treat) with baseline values as covariate. Secondary exploratory per-protocol analysis might be performed. Missing outcomes will be analysed using multiple imputation due to expected strong time trends.
The secondary outcome measures; a group difference of 6 sec. (Timed Up \& Go) and 2 cm (knee circumference) are considered clinically relevant. The statistical power is based on the calculation outlined above using the same test prerequisites.
For further details please also view the European Clinical Trials Database (EudraCT) registration:
EudraCT nr.: 2014-003395-23
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylprednisolone | Active comparator | Drug: MethylprednisolonePreoperative single high dose of Solu-Medrol 125 mg iv. |
| Isotonic Sodium Chloride | Placebo comparator | Drug: Isotonic Sodium ChloridePreoperative single dose of isotonic Sodium Chloride. |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Osteoarthrosis
- Undergoing total unilateral knee-arthroplasty surgery
- Speak and understand Danish
- Have given informed consent
Key exclusion criteria (11 listed)
- Revision, bilateral or uni chamber knee-arthroplasty surgery
- General anaesthesia
- Allergy or intolerance towards Methylprednisolone
- Local or systemic infection
- Permanent systemic treatment with steroids within 30 days preoperatively
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 |
|---|---|---|
| MethylprednisoloneAlso: Solu-MedrolComparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo) | Drug | Methylprednisolone |
| Isotonic Sodium ChloridePlacebo | Drug | Isotonic Sodium Chloride |
Primary outcome
Change in isometric knee extension strength measured as Nm/kg from baseline to 48 hours after surgery
Time frame: two days after surgery
4 secondary outcomes
Change in Timed Up & Go (sec.) from baseline (before surgery) to 48 hours after surgery
Time frame: two days after surgery
Change in knee circumference (cm) from baseline (before surgery) to 48 hours after surgery
Time frame: two days after surgery
Change in pain intensity from baseline (before surgery) to 48 hours after surgery
Time frame: two days after surgery
Change in concentration of C-reactive Protein from baseline (before surgery) to 48 hours after surgery
Time frame: two days after suregry
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 8 Apr 2016.
- Background: PubMed 23205862Husted H. Fast-track hip and knee arthroplasty: clinical and organizational aspects. Acta Orthop Suppl. 2012 Oct;83(346):1-39. doi: 10.3109/17453674.2012.700593.
- Background: PubMed 23663938Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. No abstract available.
- Background: PubMed 24359028Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP, Reed MR. Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop. 2014 Feb;85(1):26-31. doi: 10.3109/17453674.2013.874925. Epub 2013 Dec 20.
- Background: PubMed 21895500Malviya A, Martin K, Harper I, Muller SD, Emmerson KP, Partington PF, Reed MR. Enhanced recovery program for hip and knee replacement reduces death rate. Acta Orthop. 2011 Oct;82(5):577-81. doi: 10.3109/17453674.2011.618911. Epub 2011 Sep 6.
- Background: PubMed 21131371Lunn TH, Kristensen BB, Andersen LO, Husted H, Otte KS, Gaarn-Larsen L, Kehlet H. Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial. Br J Anaesth. 2011 Feb;106(2):230-8. doi: 10.1093/bja/aeq333. Epub 2010 Dec 3.
- Background: PubMed 22494947Bandholm T, Kehlet H. Physiotherapy exercise after fast-track total hip and knee arthroplasty: time for reconsideration? Arch Phys Med Rehabil. 2012 Jul;93(7):1292-4. doi: 10.1016/j.apmr.2012.02.014. Epub 2012 Feb 27.
- Background: PubMed 2315606Geborek P, Mansson B, Wollheim FA, Moritz U. Intraarticular corticosteroid injection into rheumatoid arthritis knees improves extensor muscles strength. Rheumatol Int. 1990;9(6):265-70. doi: 10.1007/BF00541322.
- Background: PubMed 19954822Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms and treatment perspectives. Semin Arthritis Rheum. 2010 Dec;40(3):250-66. doi: 10.1016/j.semarthrit.2009.10.001. Epub 2009 Dec 2.
- Background: PubMed 12437261Holte K, Kehlet H. Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications. J Am Coll Surg. 2002 Nov;195(5):694-712. doi: 10.1016/s1072-7515(02)01491-6. No abstract available.
- Results publication: PubMed 21044725Holm B, Kristensen MT, Bencke J, Husted H, Kehlet H, Bandholm T. Loss of knee-extension strength is related to knee swelling after total knee arthroplasty. Arch Phys Med Rehabil. 2010 Nov;91(11):1770-6. doi: 10.1016/j.apmr.2010.07.229.
- Individual participant dataSharing planned: Undecided
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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.
Viktoria Lindberg-Larsen, MD principal investigator
Section for Surgical Pathophysiology, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methylprednisolone and Isotonic Sodium Chloride in people with Osteoarthrosis, 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 4 inclusion and 11 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 8 Apr 2016. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Change in isometric knee extension strength measured as Nm/kg from baseline to 48 hours after surgery (time frame: two days 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 NCT02319343, which also lists 10 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 8 Apr 2016.