What side effects are associated with this type of intervention?

Common treatments for postoperative pain, such as COX-2 inhibitors like celecoxib, are associated with several side effects. These include an increased risk of cardiovascular events such as myocardial infarction and stroke, gastrointestinal issues like bleeding and ulcers, and renal complications including reduced glomerular filtration rate and potential acute renal failure. It is important for patients to be closely monitored for these adverse effects, especially if they have pre-existing conditions that may exacerbate these risks.

What prior FDA approvals exist?

Celecoxib, a COX-2 selective NSAID, has been approved by the FDA for various pain management indications, including postoperative pain. Celecoxib's efficacy in reducing pain and inflammation with a lower risk of gastrointestinal side effects compared to non-selective NSAIDs has made it a valuable option. The FDA approved celecoxib for conditions such as osteoarthritis, rheumatoid arthritis, and acute pain, including postoperative pain. The trial F14, which studies a sustained release form of celecoxib (625 mg), aims to enhance its analgesic efficacy in postoperative settings, specifically following total knee replacement surgery.

What other types of research exist?

Promising novel alternatives to F14 for postoperative pain management include: 1) Nerve growth factor (NGF) inhibitors, which target pain pathways differently than COX-2 inhibitors. 2) Disease-modifying osteoarthritis drugs (DMOADs) that are under investigation for their potential to provide pain relief and modify disease progression. 3) Bone-targeted radiopharmaceuticals like radium-223, which are being explored for their analgesic effects in bone pain. These alternatives are still under investigation but show potential for effective pain management in postoperative settings.

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F14 for Postoperative Pain After Knee Replacement

Phase 3

Waitlist Available

Research Sponsored by Arthritis Innovation Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Male and/or females indicated for primary, unilateral total knee replacement (TKR)

Absence of moderate to severe varus or valgus deformity

Must not have

Subjects with sleep apnea associated with a history of postoperative delirium. If symptomatic sleep apnea is currently treated with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP), use must be continued post-operatively

Knee surgery (including cruciate ligament, cartilage or osteotomy) other than simple arthroscopy in either knee in the last 12 months (excluding contralateral total or partial knee replacement)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests if injecting a long-lasting painkiller called celecoxib into the knee can help reduce pain for patients having knee replacement surgery. The medication works by blocking chemicals that cause pain and swelling. Celecoxib has been shown to be effective in reducing pain and improving function in patients with knee osteoarthritis.

Who is the study for?

Adults aged 45-80, with a BMI ≤ 40 kg/m2, scheduled for unilateral total knee replacement surgery can join. They must have stable health as confirmed by tests and no recent injections or major surgeries in the affected knee. Women of childbearing age need a negative pregnancy test and agree to birth control measures.

What is being tested?

The trial is testing F14 (a sustained release form of celecoxib) combined with standard pain management against standard treatment alone after knee replacement surgery. It's randomized and double-blind, meaning neither patients nor doctors know who gets which treatment.

What are the potential side effects?

Possible side effects include those typical of NSAIDs like celecoxib: stomach upset, increased risk of bleeding, kidney issues, and allergic reactions. The study will monitor safety closely.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am scheduled for a first-time knee replacement on one knee.

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My knees do not have severe inward or outward bending.

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My health is good enough for surgery according to the ASA score.

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I do not have a severe permanent bend in my joints.

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I haven't had injections in my knee for 3 months before my planned surgery.

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I can bend my joint through a range of 100 degrees.

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I am between 45 and 80 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have sleep apnea treated with CPAP or BIPAP and had postoperative delirium before.

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I haven't had major knee surgery except simple arthroscopy in the past year.

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I was diagnosed with bone tissue death in the last year.

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I have hardware in my knee from a past surgery that won't affect new knee surgery.

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I cannot stop taking opioid painkillers 7 days before surgery.

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I have pain in areas other than the study knee that needs painkillers.

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I cannot stop taking NSAIDs for 7 days before and 6 weeks after the surgery.

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I am allergic to opioids, NSAIDs, or acetaminophen.

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I have had or currently have an infection in my knee.

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I have been diagnosed with or experience seizures.

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I do not have any major surgeries planned within a year after the study surgery.

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I haven't had cancer in the last year, except for specific non-spreading skin cancers or localized cervical cancer.

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I have diabetes with an HbA1c level of 7 or higher.

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I have not had knee replacement surgery on my other knee within the last 6 months.

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I am experiencing numbness, tingling, or pain in my hands or feet.

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My other knee's pain level is 4 or higher.

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I have been diagnosed with a skin condition such as psoriasis or chronic ulcers.

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I have a history of complex regional pain syndrome.

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My mood or anxiety is stable, with a PHQ-9 score of 14 or less.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: F14 + Multimodal AnalgesiaExperimental Treatment4 Interventions

Group II: Multimodal AnalgesiaActive Control3 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Methocarbamol

2016

Completed Phase 4

~480

Acetaminophen

2017

Completed Phase 4

~2030

0 / 26Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

COX-2 inhibitors, such as celecoxib, work by selectively blocking the cyclooxygenase-2 (COX-2) enzyme, which plays a key role in the inflammatory process and pain signaling. By inhibiting COX-2, these drugs reduce the production of prostaglandins, which are compounds that cause inflammation, pain, and fever. This targeted action helps to alleviate pain and inflammation with potentially fewer gastrointestinal side effects compared to non-selective NSAIDs, which inhibit both COX-1 and COX-2 enzymes. For postoperative pain patients, this is particularly important as it can lead to effective pain management with a lower risk of adverse effects, thereby improving recovery outcomes and patient comfort. Other common treatments for postoperative pain include acetaminophen, which works centrally to reduce pain and fever, and opioids, which act on the central nervous system to block pain signals. However, COX-2 inhibitors like celecoxib are often preferred for their balance of efficacy and safety in managing postoperative pain.

Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence.