NSAIDs for Knee Osteoarthritis

Overseen By Thomas J Schnitzer, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Northwestern University

Must not be taking: Oral anticoagulants, Heparin

Disqualifiers: NSAID allergy, GI bleed, Renal insufficiency, Heart failure, others

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: Unknown

Duration: 16 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing naproxen, a common pain reliever, in people with painful knee osteoarthritis. Naproxen helps reduce swelling and pain by blocking certain chemicals in the body. Participants will receive naproxen to compare its effects. Naproxen has been shown to be an effective and well-tolerated drug for the treatment of osteoarthritis of the hip and knee in previous studies.

Do I have to stop taking my current medications for the trial?

Yes, you must be willing to discontinue current medications taken for osteoarthritis pain to participate in the trial.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current medications for osteoarthritis pain to participate in this trial.

What data supports the idea that NSAIDs for Knee Osteoarthritis is an effective treatment?

The available research shows that NSAIDs, like Naprelan and Naprosyn, are effective for treating knee osteoarthritis. In one study, both Naprelan and Naprosyn were found to be more effective than a placebo in reducing symptoms over 12 weeks. Another study confirmed that Naprelan was as effective as Naprosyn and better than a placebo. Additionally, patients who switched from a placebo to Naprelan showed significant improvement. These studies suggest that NSAIDs can effectively reduce symptoms of knee osteoarthritis. ^{1 2 3 4 5}

What data supports the effectiveness of the drug for knee osteoarthritis?

Research shows that Naprelan and Naprosyn, both forms of naproxen, are effective in treating knee osteoarthritis, with patients experiencing significant improvement compared to those taking a placebo. These studies confirm that naproxen is effective in reducing symptoms of knee osteoarthritis. ^{1 2 3 4 5}

What safety data exists for NSAIDs like naproxen in treating knee osteoarthritis?

The safety data for naproxen in treating knee osteoarthritis shows that it is generally well-tolerated. In a study comparing Naprelan and Naprosyn, both formulations were found to have similar efficacy, with Naprosyn showing more drug-related adverse events, particularly gastrointestinal issues, compared to placebo. Another study comparing naproxen with aceclofenac found that naproxen had a higher incidence of adverse effects, especially gastrointestinal side effects. Overall, naproxen is effective but may have more gastrointestinal side effects compared to some alternatives. ^{2 3 6 7 8}

Is naproxen safe for treating knee osteoarthritis?

Naproxen, used in various forms like Naprelan and Naprosyn, has been shown to be generally safe for treating knee osteoarthritis, though some patients may experience gastrointestinal side effects. In studies, it was found to have a similar safety profile to other treatments, with no serious side effects reported. ^{2 3 6 7 8}

Is the drug Naproxen a promising treatment for knee osteoarthritis?

Yes, Naproxen is a promising drug for treating knee osteoarthritis. It has been shown to effectively reduce pain and improve joint function in patients. While it is comparable to other treatments like aceclofenac, it is effective in managing symptoms of osteoarthritis. ^{1 5 7 9 10}

How does naproxen differ from other drugs for knee osteoarthritis?

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that helps reduce pain and inflammation in knee osteoarthritis, and it is often compared to other NSAIDs like celecoxib and aceclofenac. While it is effective, some studies suggest that aceclofenac may have fewer gastrointestinal side effects, and topical NSAIDs might be preferred for those who cannot tolerate oral NSAIDs. ^{1 5 7 9 10}

Research Team

Thomas Schnitzer

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for men and women over 40 with painful knee osteoarthritis, experiencing moderate pain levels. Participants must be willing to stop current OA pain medications, use birth control if applicable, maintain any non-drug therapies stable, and have access to a cellphone or computer for eDiary entries.

Inclusion Criteria

eDiary entries on at least 4 out 7 days per week during the observation period

I have been diagnosed with knee osteoarthritis.

I am over 40 years old.

Exclusion Criteria

My back pain is worse than my arthritis pain.

I have had a nerve ablation for knee pain.

I haven't had any biological injections in the affected area in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 4-period double-cross-over design with 2 weeks of treatment with either naproxen or placebo, followed by 2 weeks of washout, repeated 4 times

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Naproxen
• Placebo

Trial Overview The study tests the effectiveness of Naproxen (an NSAID) against a placebo in managing knee osteoarthritis pain. It's designed as a pilot with four periods where participants switch between treatments and placebos without knowing which they're receiving.

Participant Groups

Group I: Cross-over Treatment: Initial treatment with placebo Experimental Treatment 2 Interventions

There will be a 4 period cross-over: 2 weeks of treatment with IP, followed by 2 weeks of washout, and this repeated 3 more times. Treatment will be such that all participants will receive 2 treatment periods with naproxen and 2 treatment periods with placebo. The order of treatment will be randomized and the treatment allocation and IP will be blinded.

Group II: Cross-over Treatment: Initial treatment with naproxen Experimental Treatment 2 Interventions

There will be a 4 period cross-over: 2 weeks of treatment with IP, followed by 2 weeks of washout, and this repeated 3 more times. Treatment will be such that all participants will receive 2 treatment periods with naproxen and 2 treatment periods with placebo. The order of treatment will be randomized and the treatment allocation and IP will be blinded.

Naproxen is already approved in United States, Canada, European Union, United Kingdom for the following indications:

Approved in United States as Naprosyn for:

• Painful knee osteoarthritis
• Arthritis
• Menstrual pain
• Muscle and joint inflammation
• Gout

Approved in United States as Aleve for:

• Pain relief
• Fever reduction
• Headache

Approved in Canada as Naprelan for:

• Painful knee osteoarthritis
• Arthritis
• Menstrual pain

Approved in European Union as Naprosyn for:

• Painful knee osteoarthritis
• Arthritis
• Menstrual pain
• Muscle and joint inflammation
• Gout

Approved in United Kingdom as Feminax Ultra for:

• Primary dysmenorrhoea

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

In a 53-week study involving 1,020 patients with knee osteoarthritis, both doses of naproxcinod (375 mg and 750 mg) showed significantly greater improvements in pain and function compared to placebo at 13 weeks.

Naproxcinod 750 mg was found to be as effective as naproxen 500 mg, indicating it is a viable alternative for treating osteoarthritis, and it was well tolerated with no significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of naproxcinod in patients with osteoarthritis of the knee: a 53-week prospective randomized multicenter study. Schnitzer, TJ., Hochberg, MC., Marrero, CE., et al.[2013]

In a study involving 347 patients with knee osteoarthritis, Naprelan (1,000 mg once daily) was found to be equally effective as Naprosyn (500 mg twice daily) in reducing symptoms, with both showing significant benefits over placebo after 12 weeks.

Naprelan had a better safety profile, as it did not show a significant increase in adverse events compared to placebo, while Naprosyn was associated with more drug-related adverse events, particularly gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of Naprelan and Naprosyn in the treatment of osteoarthritis of the knee. Schiff, MH.[2013]

In a study involving 444 patients with knee osteoarthritis, both naproxen sodium (660 mg and 440 mg for older patients) and ibuprofen (1200 mg) were found to significantly relieve pain compared to placebo, with naproxen showing a greater reduction in symptoms overall.

Naproxen sodium was particularly effective for night-time pain relief and improved all assessed symptoms compared to placebo, while both medications had similar safety profiles with no significant differences in adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic efficacy and safety of nonprescription doses of naproxen sodium and Ibuprofen in the treatment of osteoarthritis of the knee. Schiff, M., Minic, M.[2022]

In a study involving 367 Asian patients with knee osteoarthritis, celecoxib was found to be as effective as naproxen in reducing pain, with both treatments showing significant improvements compared to placebo.

Celecoxib demonstrated a better safety profile, with a lower incidence of treatment-related adverse events (13%) compared to naproxen (24%), indicating it is a well-tolerated option for managing knee OA in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nonsteroidal anti-inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo-controlled study. Essex, MN., O'Connell, MA., Behar, R., et al.[2022]

In a 6-month study involving 586 patients with knee osteoarthritis, celecoxib showed similar efficacy to naproxen, with 52.7% of celecoxib patients achieving a significant improvement in symptoms compared to 49.7% for naproxen.

Celecoxib was associated with significantly fewer gastrointestinal side effects, with only 4.1% of patients discontinuing treatment due to these issues, compared to 15.1% for those taking naproxen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of celecoxib versus naproxen in patients with osteoarthritis of the knee: a randomized, double-blind, double-dummy trial. Essex, MN., Bhadra, P., Sands, GH.[2022]

In a six-week study involving 85 patients with osteoarthritis, Flurbiprofen-SR 200 mg showed similar efficacy to Diclofenac Sodium-SR 100 mg, with no significant differences in treatment outcomes.

Both medications had comparable tolerability and safety profiles, as there were no significant differences in adverse events or treatment terminations between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind randomized controlled trial of flurbiprofen-SR (ANSAID-SR) and diclofenac sodium-SR (Voltaren-SR) in the treatment of osteoarthritis. Bellamy, N., Bensen, WG., Ford, PM., et al.[2013]

In a 12-week clinical trial involving 374 patients with active knee osteoarthritis, aceclofenac (100 mg twice daily) was found to be as effective as naproxen (500 mg twice daily) in reducing pain and improving knee function, with 76-86% of aceclofenac patients reporting pain reduction.

Aceclofenac demonstrated better tolerability than naproxen, with fewer adverse effects (12.6% vs. 16.3%), particularly in terms of gastrointestinal side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aceclofenac is a well-tolerated alternative to naproxen in the treatment of osteoarthritis. Kornasoff, D., Frerick, H., Bowdler, J., et al.[2019]

In a study of 307 patients over 12 weeks, tenoxicam demonstrated a lower incidence of adverse events (29.0%) compared to ketoprofen (47.3%), indicating it may be a safer option for treating osteoarthritis.

Both tenoxicam and ketoprofen showed similar efficacy in managing osteoarthritis symptoms, with no significant differences in overall treatment outcomes, suggesting that tenoxicam offers a favorable balance of effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised double-blind multicentre trial comparing tenoxicam and ketoprofen in osteoarthritis. Ejstrup, L., Knudsen, JV., Petersen, L.[2019]

Topical NSAIDs are effective for treating knee and hand osteoarthritis as well as acute musculoskeletal pain, and they are recommended in various clinical guidelines due to their efficacy and safety profile.

These medications have fewer systemic side effects compared to oral NSAIDs, making them a preferable first option, especially for patients who cannot take oral NSAIDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Topical NSAIDs: ineffective or undervalued?] van Herwaarden, N., van den Elsen, GAH., de Jong, ICA., et al.[2021]

In a clinical trial involving 600 patients with knee osteoarthritis, celecoxib (200 mg daily) was found to be as effective as diclofenac (150 mg daily) in relieving pain and symptoms, with both medications showing significant improvement compared to placebo.

Celecoxib demonstrated a superior safety profile, with fewer gastrointestinal side effects and no significant elevations in liver enzymes or reductions in hemoglobin levels, which were observed in patients taking diclofenac.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celecoxib versus diclofenac in the management of osteoarthritis of the knee. McKenna, F., Borenstein, D., Wendt, H., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of naproxcinod in patients with osteoarthritis of the knee: a 53-week prospective randomized multicenter study. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

A comparison of Naprelan and Naprosyn in the treatment of osteoarthritis of the knee. [2013]

3. Canada pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic efficacy and safety of nonprescription doses of naproxen sodium and Ibuprofen in the treatment of osteoarthritis of the knee. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nonsteroidal anti-inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo-controlled study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of celecoxib versus naproxen in patients with osteoarthritis of the knee: a randomized, double-blind, double-dummy trial. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

Double-blind randomized controlled trial of flurbiprofen-SR (ANSAID-SR) and diclofenac sodium-SR (Voltaren-SR) in the treatment of osteoarthritis. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Aceclofenac is a well-tolerated alternative to naproxen in the treatment of osteoarthritis. [2019]

8. Norway pubmed.ncbi.nlm.nih.gov

A randomised double-blind multicentre trial comparing tenoxicam and ketoprofen in osteoarthritis. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

[Topical NSAIDs: ineffective or undervalued?] [2021]

10. England pubmed.ncbi.nlm.nih.gov

Celecoxib versus diclofenac in the management of osteoarthritis of the knee. [2022]