Corticosteroid Injection for Knee Arthritis

(COSTI Trial)

Overseen By Cassandra Tardif-Theriault, BKin

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Unity Health Toronto

Disqualifiers: Inflammatory arthritis, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: Peri-operative

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a corticosteroid injection in the knee can improve outcomes for people undergoing total knee arthroplasty (TKA), a surgery for severe knee arthritis. The study compares the effects of the injection with a placebo (a treatment with no active drug) to determine if it reduces pain and improves knee function after surgery. Participants must have a diagnosis of primary osteoarthritis and significant pain in the opposite knee from where they will have surgery. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that corticosteroid injections can provide short-term relief for knee osteoarthritis, which affects the knee joint. Some studies found that these injections reduce symptoms for up to two weeks, while other research suggests improvement for up to 12 weeks. However, concerns exist about their long-term safety. One study noted that repeated steroid injections might cause more damage to the knee joint over time. Overall, corticosteroid injections are generally considered safe and effective for short-term use, but opinions vary on their long-term effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the corticosteroid injection for knee arthritis because it combines an effective anti-inflammatory steroid, methylprednisolone, with a local anesthetic, bupivacaine, to target pain and inflammation directly at the knee joint. Unlike standard treatments that may involve oral medications or physical therapy, this approach delivers the medication directly into the joint space using ultrasound guidance, potentially offering more precise relief. This method could provide quicker and more targeted pain relief, with the added benefit of reduced systemic side effects. Additionally, the use of ultrasound guidance ensures accuracy in delivering the treatment exactly where it's needed most.

What evidence suggests that contralateral corticosteroid injection might be an effective treatment for knee arthritis?

Research has shown that corticosteroid injections can reduce pain and improve movement in people with knee arthritis. In this trial, participants in Group A will receive an 80mg injection of methylprednisolone, which studies have shown can relieve symptoms for up to 12 weeks. One study demonstrated that methylprednisolone effectively reduced pain and improved mobility. However, evidence also suggests that these injections might worsen knee arthritis over time. While the treatment can offer short-term relief, considering possible long-term effects is important. Participants in Group B will receive a sham comparator involving band-aid placement to assess the placebo effect. ^{1 6 7 8 9}

Who Is on the Research Team?

Amir Khoshbin, MD, FRCS (C)

Principal Investigator

Unity Health Toronto

Are You a Good Fit for This Trial?

This trial is for individuals with knee osteoarthritis who are scheduled for total knee replacement surgery. Participants should not have any known allergies to corticosteroids or bupivacaine, and must be willing to undergo the study procedures.

Inclusion Criteria

I haven't had injections in the opposite knee within the last year.

I have pain in the opposite knee with a score over 4 out of 10.

Patient is able to read and understand English and provide informed consent to participation in the study

Exclusion Criteria

Cognitive impairment (dementia, Alzheimer's, uncontrolled delirium) which will prevent patients from completing primary outcome measure or comply with follow-up requirements

I have had knee surgery, such as a total knee replacement or fracture repair.

I have had knee surgery before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a contralateral corticosteroid injection or a sham band-aid application during the peri-operative period for TKA

Peri-operative

1 visit (in-person)

Follow-up

Participants are monitored for pain, function, and quality of life using various outcome measures

1 year

4 visits (in-person) at 4, 8, 12 weeks and 1 year post-surgery

What Are the Treatments Tested in This Trial?

Interventions

• Contralateral Corticosteroid Injection

Trial Overview The study tests if a corticosteroid injection in the opposite knee can help reduce pain and improve function after knee replacement surgery. It's a triple-blinded trial, meaning neither patients, doctors nor assessors know who receives the real treatment.

How Is the Trial Designed?

Group I: Group A - Corticosteroid Injection Experimental Treatment 1 Intervention

Corticosteroid injection - 80mg methylprednisolone (total volume 2ml) with 6 mL of 1% Bupivacaine without epinephrine (Total Volume 8 mL). The patient will be brought to the regional room where a fully licensed anaesthesiologist will perform standard of care anaesthesia followed by an ultrasound guided intra-articular knee injection with steroid AFTER the spinal neuraxial blockage has already been administered.

Group II: Group B - Band-Aid Placement Placebo Group 1 Intervention

The patient will be brought to the regional room where a fellowship trained interventional pain/regional anaesthesiologist will perform standard of care anaesthesia followed by the application of a band-aid.

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Published Research Related to This Trial

Local corticosteroid injections are generally safe and can effectively manage symptoms in conditions like rheumatoid arthritis and knee osteoarthritis, providing relief for up to three months in some cases.

While these injections can help with acute flare-ups and certain symptoms, they do not significantly prevent joint damage or erosive changes, and their use should complement other treatments like physical therapy and disease-modifying drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-articular corticosteroids. An updated assessment. Gray, RG., Gottlieb, NL.[2006]

Corticosteroid injections for knee disorders like osteoarthritis and rheumatoid arthritis have been used since the 1950s and are effective for rapid symptom relief while minimizing systemic side effects.

The technique for administering intra-articular knee injections is straightforward and can be performed quickly in both office and hospital settings, making it accessible for treating acute or severe symptom flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injectable corticosteroids in treatment of arthritis of the knee. Schumacher, HR., Chen, LX.[2022]

Corticosteroid knee injections provide short-term symptomatic relief for knee osteoarthritis, but their effectiveness is limited to this short duration, with no long-term benefits supported by evidence.

The accuracy of these injections can be problematic, with up to 20% of procedures failing to place the steroid correctly in the joint, and the risk of serious infectious complications can be as high as 1 in 3,000, especially in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy, accuracy and complications of corticosteroid injections of the knee joint. McGarry, JG., Daruwalla, ZJ.[2021]

In a study involving 60 patients undergoing bilateral total knee arthroplasty, the use of a multimodal cocktail injection with corticosteroids did not show significant differences in pain relief, motion range, or swelling compared to injections without corticosteroids.

The findings suggest that multimodal periarticular injections without corticosteroids can effectively manage postoperative pain and swelling, indicating that corticosteroids like betamethasone may not be necessary for optimal outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Efficacy of Corticosteroids as an Adjuvant for Periarticular Cocktail Injection in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Double-Blind Controlled Trial. Peng, H., Wang, W., Lin, J., et al.[2021]

Corticosteroid injections are the most common treatment for osteoarthritis in the knee, but there is still debate among practitioners about their effectiveness and the best corticosteroid to use.

No consensus has been reached on the optimal corticosteroid type, dosage, or injection frequency, suggesting that treatment should be personalized based on individual patient needs and responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroid injection into the osteoarthritic knee: drug selection, dose, and injection frequency. Douglas, RJ.[2012]

In a study of 3,822 patients with or at risk of knee osteoarthritis, those who received corticosteroid injections had a significantly higher risk of needing knee arthroplasty, with 31.3% undergoing surgery compared to only 5.0% of those who did not receive injections.

Each corticosteroid injection increased the absolute risk of knee arthroplasty by 9.4% over nine years, suggesting that these injections may harm the joint and accelerate the progression of osteoarthritis, leading to a recommendation for more conservative treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-articular corticosteroid injections increase the risk of requiring knee arthroplasty. Wijn, SRW., Rovers, MM., van Tienen, TG., et al.[2020]

Intra-articular injections of ketorolac and corticosteroids both provided significant pain relief and functional improvement in patients with knee osteoarthritis, with no significant differences in outcomes between the two treatments after 3 months.

While corticosteroid injections showed slightly better pain relief in the first week, both treatments resulted in similar success rates, indicating that ketorolac can be a safe alternative to corticosteroids for managing knee OA symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Intra-articular Ketorolac Versus Corticosteroid Injection for Knee Osteoarthritis: A Retrospective Comparative Study. Xu, J., Qu, Y., Li, H., et al.[2022]

Corticosteroid injections can lead to side effects ranging from mild skin reactions and flare responses to serious complications like infections, tendon ruptures, and osteonecrosis.

Patients with diabetes should be cautious, as corticosteroids can affect blood glucose levels, and there is also a risk of visual side effects related to central serous chorioretinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications Associated with Intra-Articular and Extra-Articular Corticosteroid Injections. Honcharuk, E., Monica, J.[2021]

Intraarticular corticosteroid injections are a common treatment for knee pain due to osteoarthritis, positioned between conservative treatments like ice therapy and more invasive options like knee replacement surgery.

The paper discusses various types of corticosteroids and their combinations with local anesthetics, highlighting the flexibility in treatment approaches for managing knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current concepts on the use of corticosteroid injections for knee osteoarthritis. Law, TY., Nguyen, C., Frank, RM., et al.[2022]

Intra-synovial corticosteroids are a rapid and effective treatment for juvenile chronic arthritis (JCA), particularly beneficial for limited joint involvement while waiting for disease-modifying drugs to take effect.

While generally safe, there are important contraindications and potential complications, such as infection and joint damage, emphasizing the need for proper injection technique and post-injection care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-synovial corticosteroid injections in juvenile chronic arthritis--a review. See, Y.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10570668/

Corticosteroid Injections for Symptomatic Treatment ... Corticosteroid injections demonstrated clinically meaningful improvements in KOA symptoms over 12 weeks of follow‐up. These data support larger ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1743919118306265

Review Comparison of intra-articular hyaluronic acid and ... Both HA and methylprednisolone injections were effective therapies for patients with knee OA. Methylprednisolone showed comparable efficacy in reducing pain and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5608740/

COMPARED EFFICACY OF INTRA-ARTICULAR ... Our study demonstrated that both intra-articular triamcinolone and methylprednisolone are effective at reducing pain and improving function in patients with ...

4. rsna.org rsna.org/media/press/i/2386

Steroid Injections Worsen Knee Arthritis Statistical analysis showed that corticosteroid knee injections were significantly associated with the overall progression of osteoarthritis in ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1905877

Physical Therapy versus Glucocorticoid Injection for ... Patients with osteoarthritis of the knee who underwent physical therapy had less pain and functional disability at 1 year than patients who received an ...

6. rsna.org rsna.org/news/2025/may/knee-arthritis-made-worse

Knee Arthritis Made Worse with Steroid Injections The study found that corticosteroid injections led to more knee joint damage over the two-year period than both the control group and those who ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772654123000818

Debate: Intra-articular steroid injections for osteoarthritis In conclusion, IACS injection has not clearly demonstrated long-term efficacy for treating joint pains in knee or hip OA. IACS injection is not totally safe, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC387479/

Corticosteroid injections for osteoarthritis of the knee Conclusion Evidence supports short term (up to two weeks) improvement in symptoms of osteoarthritis of the knee after intra-articular corticosteroid injection.

9. journals.lww.com journals.lww.com/md-journal/fulltext/2018/04130/intra_articular_injection_of_methylprednisolone.8.aspx

Intra-articular injection of methylprednisolone for... : Medicine He et al concluded that corticosteroid was found to be an effective and safe therapy in the treatment of knee OA compared with other intra-articular injections.