Triamcinolone + Ketorolac for Knee Osteoarthritis

(TriKe Trial)

Overseen By Benjamin Kammerman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: United Health Services Hospitals, Inc.

Must not be taking: Opioids, Systemic steroids

Disqualifiers: Uncontrolled diabetes, Kidney disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for knee osteoarthritis by testing different injections. It examines ketorolac, a non-steroidal anti-inflammatory drug, as an alternative or addition to cortisone, which is commonly used but can cause side effects like tissue damage. The trial compares the effects of ketorolac alone, cortisone (triamcinolone acetonide) alone, and a combination of both to determine the most effective option. Suitable participants have knee pain due to osteoarthritis and have not recently undergone knee injections or surgery. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiming to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used systemic steroids or opioids in the last 3 months.

What is the safety track record for these treatments?

Research has shown that ketorolac, when injected into joints, is safe and works similarly to traditional steroid injections like triamcinolone. Studies have found that ketorolac causes less damage to joint cells than steroids and is just as effective, suggesting it might be a safer choice for long-term use.

Triamcinolone, a type of steroid, often treats joint pain and swelling. Most people tolerate it well, but some may experience side effects like thinning of the tissue near the injection site, especially with repeated use.

In studies where ketorolac is mixed with ropivacaine (a pain reliever), the combination improved pain relief without major safety issues. This extra pain relief is promising for those considering this treatment.

Overall, research supports that both ketorolac and triamcinolone are well-tolerated for joint injections, with ketorolac possibly being a safer long-term option. However, discussing any treatment options with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for knee osteoarthritis because they combine well-known pain relief and anti-inflammatory medications with local anesthetics, potentially offering quicker and more targeted relief. Unlike standard treatments that often include oral NSAIDs or corticosteroid injections alone, the trial combines Triamcinolone acetonide and Ketorolac with Ropivacaine for direct injection into the knee. This combination might deliver more immediate pain relief while reducing inflammation directly at the site. By using this method, the treatments aim to minimize systemic side effects and enhance the overall effectiveness of managing osteoarthritis symptoms.

What evidence suggests that this trial's treatments could be effective for knee osteoarthritis?

Research has shown that triamcinolone acetonide can significantly reduce knee osteoarthritis pain over 24 weeks, offering better relief than a placebo. In this trial, one treatment arm will test the combination of triamcinolone acetonide, ketorolac, and ropivacaine. Another arm will explore ketorolac combined with ropivacaine and normal saline. Studies indicate that ketorolac injections can provide pain relief similar to triamcinolone, with effects lasting up to 6 months. When combined with ropivacaine, ketorolac reduces pain shortly after injection and for several hours afterward. Researchers are investigating the combination of triamcinolone and ketorolac because both are effective individually. This combination might enhance results or reduce side effects compared to using each one separately. ^{1 2 3 4 6}

Who Is on the Research Team?

Stanley Hunter, MD

Principal Investigator

United Health Services Hospitals, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 21 with knee pain from osteoarthritis, who can speak English well enough to fill out surveys. They must have had weight-bearing x-rays within the last year to check their arthritis stage and be willing to complete follow-up surveys.

Exclusion Criteria

I haven't taken steroids in the last 3 months.

My diabetes is not under control.

I have not had a knee injection in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intra-articular injection of either ketorolac, triamcinolone, or a combination of both into the affected knee joint/s

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with surveys completed at 1 week, 6 weeks, 12 weeks, and possibly 24 weeks post-injection

24 weeks

4 visits (virtual or in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac
• Ropivacaine
• Triamcinolone acetonide

Trial Overview The trial is testing injections into the knee joint: one with a cortisone drug called Triamcinolone, another with an anti-inflammatory called Ketorolac, and a mix of both. It aims to see if Ketorolac alone or combined with Triamcinolone works better than just Triamcinolone for knee arthritis.

How Is the Trial Designed?

Group I: Triamcinolone acetonide - Ketorolac - Ropivacaine Experimental Treatment 1 Intervention

Subject would receive: Triamcinolone acetonide, 40 mg/mL Ketorolac 30 mg/mL, 1 mL Ropivacaine 0.2%, 2 mL for a total of 4 mL injected intraarticularly into affected knee/s at randomization

Group II: Ketorolac - Ropivacaine - Normal Saline Experimental Treatment 1 Intervention

Subject would receive: Ketorolac 30 mg/mL, 1 mL Ropivacaine 0.2%, 2 mL Saline 0.9% 1 mL for a total of 4 mL injected intraarticularly into affected knee/s at randomization

Group III: Triamcinolone acetonide - Ropivacaine - Normal Saline Active Control 1 Intervention

Subject would receive: Triamcinolone acetonide, 40 mg/mL. 1 mL Ropivacaine 0.2%, 2 mL Saline 0.9% 1 mL for a total of 4 mL injected intraarticularly into affected knee/s at randomization

Ketorolac is already approved in United States, European Union, Switzerland for the following indications:

Approved in United States as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea
• Idiopathic pericarditis
• Ocular itching

Approved in European Union as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea

Approved in United States as Acular for:

• Ocular itching
• Inflammation after eye surgery

Approved in United States as Sprix for:

• Moderate to severe pain

Approved in Switzerland as Ketorolac for:

• Moderate to severe pain
• Postoperative pain

Who Is Running the Clinical Trial?

United Health Services Hospitals, Inc.

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

Triamcinolone acetonide extended-release (ER) 32 mg significantly reduces knee osteoarthritis pain over 24 weeks compared to placebo, while also improving stiffness and physical function, demonstrating its efficacy as a treatment option.

The formulation of triamcinolone acetonide ER in PLGA microspheres allows for prolonged release in the joint, minimizing systemic exposure and related side effects, making it a safer alternative to traditional corticosteroid injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. Paik, J., Duggan, ST., Keam, SJ.[2023]

Intraarticular injection of triamcinolone hexacetonide (TH) combined with lidocaine (LD) significantly improved pain during movement and reduced joint swelling in patients with osteoarthritis of the hand interphalangeal joints compared to lidocaine alone, with results observed as early as one week after treatment.

The study involved 60 patients, primarily women with an average age of 60.7 years, and found no significant adverse effects from the treatment, indicating that TH/LD is a safe and effective option for managing symptoms of osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Triamcinolone Hexacetonide Intraarticular Injection in Interphalangeal Joints: A 12-week Randomized Controlled Trial in Patients with Hand Osteoarthritis. Spolidoro Paschoal, Nde O., Natour, J., Machado, FS., et al.[2017]

In a study involving 15 rabbits, intraocular injections of preservative-free ketorolac tromethamine showed no significant adverse effects on retinal function or intraocular pressure compared to control eyes, indicating its safety for use.

The drug had a short elimination half-life of 2.3 hours in the vitreous, and no histopathological changes were observed, suggesting that ketorolac could be a viable alternative to steroid injections for treating intraocular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of intraocular ketorolac in rabbits. Margalit, E., Kugler, LJ., Brumm, MV., et al.[2022]

In a study of 88 women experiencing preterm labor at less than 32 weeks of gestation, ketorolac was found to be more effective than magnesium sulfate in stopping labor, with an average time of 2.71 hours compared to 6.22 hours for magnesium sulfate.

Both treatments were safe, as no patients had to stop taking either medication due to side effects, and there were no differences in neonatal complications between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor. Schorr, SJ., Ascarelli, MH., Rust, OA., et al.[2019]

Intra-articular injections of triamcinolone hexacetonide (TAH) and triamcinolone acetonide (TA) significantly raised blood glucose levels in patients with controlled diabetes and symptomatic osteoarthritis of the knee, with peak levels observed 24 to 32 hours post-injection.

In contrast, patients receiving hyaluronic acid (HA) injections did not experience significant increases in blood glucose, indicating that the rise in glucose levels is specifically associated with the steroid injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of intra-articular triamcinolone preparations on blood glucose levels in diabetic patients: a controlled study. Habib, GS., Miari, W.[2022]

In a study involving 85 children with oligoarticular juvenile idiopathic arthritis, intra-articular triamcinolone hexacetonide (TH) was found to be significantly more effective than triamcinolone acetonide (TA) in reducing joint inflammation, with response rates of 81.4% for TH compared to 53.3% for TA at 6 months.

The effectiveness of TH over TA was consistent over 24 months, indicating that TH may provide better long-term relief for patients, regardless of their disease duration or inflammation levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligoarticular juvenile idiopathic arthritis. Zulian, F., Martini, G., Gobber, D., et al.[2015]

In a study of 60 osteoarthritis patients receiving intra-articular injections, triamcinolone hexacetonide combined with lidocaine significantly reduced joint swelling and decreased the need for pain relief medication over 48 weeks.

However, the treatment did not show any impact on the radiographic progression of osteoarthritis in the injected joints, indicating that while it helps with symptoms, it does not alter the underlying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-articular triamcinolone hexacetonide injections in hands osteoarthritis ‒ A double-blinded randomized controlled trial with a one year follow-up. Paschoal, NOS., Natour, J., Machado, FS., et al.[2022]

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory drug (NSAID) used for pain management, particularly in emergency and postoperative settings, but it can lead to acute renal failure and hyperkalemia in susceptible individuals.

In three reported cases, patients with risk factors for kidney issues developed these complications after receiving moderate doses of ketorolac, but both conditions were reversible upon stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. Haragsim, L., Dalal, R., Bagga, H., et al.[2019]

In a multicenter study involving patients with moderate to severe inflammation after cataract surgery, ketorolac tromethamine 0.5% was significantly more effective than a placebo in reducing inflammation and associated symptoms like pain and photophobia.

The treatment was found to be safe, with no significant differences in visual acuity or adverse events compared to the placebo, indicating that ketorolac is a reliable option for managing post-surgical inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. Heier, J., Cheetham, JK., Degryse, R., et al.[2019]

In a study of 82 patients with knee osteoarthritis, hyaluronic acid (HA) showed significantly better outcomes for pain relief and functionality compared to intraarticular triamcinolone hexacetonide at six months.

Both treatments had similar effects in the first 12 weeks, but the steroid group's effectiveness declined rapidly after that, indicating that HA may provide more sustained benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-articular hyaluronic acid is superior to steroids in knee osteoarthritis: A comparative, randomized study. Vaishya, R., Pandit, R., Agarwal, AK., et al.[2020]

In a phase 3b study involving 208 patients with knee osteoarthritis, repeat injections of triamcinolone acetonide extended-release (TA-ER) were found to be safe and well tolerated, with no unexpected adverse events or significant changes in knee radiographs after 52 weeks.

Both the first and second injections of TA-ER provided similar and substantial pain relief, with most patients experiencing at least a 50% reduction in pain, indicating effective symptom management across varying severities of osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Repeat Administration of Triamcinolone Acetonide Extended-release in Osteoarthritis of the Knee: A Phase 3b, Open-label Study. Spitzer, AI., Richmond, JC., Kraus, VB., et al.[2020]

A significant portion of ketorolac use in Italy is off-label, with 553 out of 822 reported cases of suspected adverse drug reactions (ADRs) classified as off-label, indicating a widespread practice that raises safety concerns.

Off-label use of ketorolac is associated with a higher incidence of serious ADRs (58.6%) compared to on-label use (39.0%), particularly gastrointestinal events, highlighting the need for careful monitoring and regulation by health authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions associated with off-label use of ketorolac, with particular focus on elderly patients. An analysis of the Italian pharmacovigilance database and a population based study. Viola, E., Trifirò, G., Ingrasciotta, Y., et al.[2018]

In a study involving 100 patients with knee osteoarthritis, both triamcinolone hexacetonide (TH) and methylprednisolone acetate (MA) injections significantly reduced pain at 4 weeks, with sustained improvements observed up to 24 weeks.

There was no significant difference in efficacy between TH and MA, as both treatments showed similar outcomes in pain relief and functional improvement, indicating that either corticosteroid can be effectively used for managing knee OA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Triamcinolone Hexacetonide versus Methylprednisolone Acetate Intraarticular Injections in Knee Osteoarthritis: A Randomized, Double-blinded, 24-week Study. Lomonte, AB., de Morais, MG., de Carvalho, LO., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4616973/

Comparison of the effects of intra-articular sole ropivacaine ... Results: All groups had excellent analgesia at 0 and 4 hours, postoperatively. Group-combined ketorolac and ropivacaine had significantly lower visual analogue ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2352344119300494

Effectiveness of intraoperative periarticular cocktail ... Results. The cocktail injected knee had significantly less pain when compared with the control knee during the first 48 hours and significantly shorter period ...

3. journal-cot.com journal-cot.com/article/S0976-5662(24)00273-X/fulltext

Efficacy of the combination of intra-articular ropivacaine ... Result: The mean VAS score 4 hours after the intervention was 1.59±0.94, after 8 hours it was 2.25±1.19 which then dropped to 2.03±1.03 at 20 hours, 2.56±1.24 ...

4. oarsijournal.com oarsijournal.com/article/S1063-4584(25)00780-0/fulltext

EFFICACY AND SAFETY OF ANALGESICS IN THE ... Following HR, only local ropivacaine combined with ketorolac and adrenaline (SMD -1.28, 95% CrI -1.83 to -0.75) reached MCID with a 99% probability (Fig 3).

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pmrj.13387

Corticosteroid versus ketorolac injection for treatment of ... IA ketorolac can provide rapid relief, with effects seen as early as 1-hour post injection, and its efficacy can last up to 6 months. Therefore, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7031550/

Influence of Ketorolac Supplementation on Pain Control for ... Our meta‐analysis suggests that compared to control intervention for knee arthroscopy, ketorolac supplementation can favorably reduce pain scores at 1 h and 2 ...