Opioids vs Non-Opioids for Postoperative Pain After Knee Surgery

Overseen By Katie Jensen

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sanford Health

Must not be taking: Anticoagulants

Disqualifiers: Chronic opioid use, Substance abuse, Chronic pain, 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: 4

Duration: 6 weeks

148 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to manage pain after knee surgery by comparing opioids (strong painkillers) with non-opioids like ibuprofen and acetaminophen. Researchers aim to determine if non-opioids can relieve pain as effectively as opioids and how each type affects individuals based on factors like gender and job status. It is ideal for those undergoing elective arthroscopic knee surgery, such as a partial meniscectomy, who have not used opioids long-term and do not have chronic pain or substance abuse issues. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand how it benefits 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 are taking certain blood thinners or medications that increase bleeding, except for low-dose aspirin (ASA 81mg).

What is the safety track record for these treatments?

A previous study found that acetaminophen, a common pain reliever, effectively reduces pain without major side effects. However, high doses or combining it with alcohol can seriously harm the liver. Research has shown that ibuprofen, another pain reliever, is generally safe but may cause stomach ulcers or heart problems with long-term use.

For opioids like hydrocodone (found in Norco), studies indicate they effectively manage severe pain but carry risks such as addiction and overdose. Most side effects can be managed, but following dosing instructions carefully is crucial. Overall, these medications are widely used and well-researched for pain management, but each has potential risks. Always consider these factors and consult a healthcare provider about any concerns before joining a study. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore alternatives to opioids for managing postoperative pain after knee surgery. Unlike opioids, which are powerful but come with risks like addiction and side effects, the non-opioid group uses acetaminophen and ibuprofen, which are known for their safety and fewer side effects. These non-opioid options could offer effective pain relief without the concerns associated with opioids, making recovery smoother and safer for patients.

What evidence suggests that this trial's treatments could be effective for postoperative pain after knee surgery?

This trial will compare the effectiveness of opioids and non-opioids for postoperative pain after knee surgery. Research has shown that ibuprofen, which participants in the non-opioid arm may receive, can be as effective as oral morphine for pain relief after minor bone surgeries. It helps reduce pain and the need for opioids after surgery. Studies have found that while acetaminophen, another non-opioid option in this trial, is often used, it might not be as effective for pain relief after knee surgeries. However, it can help lower opioid use and reduce side effects like vomiting. Participants in the opioid arm may receive hydrocodone, a strong painkiller for moderate-to-severe pain, which requires careful use to avoid overuse. Each option has its benefits, and effectiveness can depend on individual needs and conditions. ^{1 3 6 7 8}

Who Is on the Research Team?

Bruce Piatt, MD

Principal Investigator

Sanford Health

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 undergoing elective knee arthroscopy, like meniscectomy or loose body removal. It's not for those with a history of chronic opioid use, significant medical issues in the past year, pregnant/nursing women, or anyone unable to consent. People on certain blood thinners or with active ulcers are also excluded.

Inclusion Criteria

I am scheduled for knee surgery to remove or repair damaged tissue or loose fragments.

Exclusion Criteria

I have been diagnosed with cognitive impairment.

I am scheduled for knee ligament reconstruction surgery.

I have chronic pain that lasts a long time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either opioid or non-opioid medications for pain management after knee arthroscopy

6 weeks

Daily monitoring for 2 weeks, follow-up at 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Follow-up assessments at 2 weeks and 6 weeks post-operatively

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen 325Mg Tab
• Ibuprofen 600 mg
• Norco 5Mg-325Mg Tablet

Trial Overview

The study compares pain management using opioids (Norco) versus non-opioids (Ibuprofen and Acetaminophen) after knee surgery. It aims to see if non-narcotics can match narcotics' pain relief and how patient characteristics influence post-surgery pain and medication effectiveness.

How Is the Trial Designed?

Group I: Opioid Active Control 1 Intervention

Group II: Non-opioid Active Control 2 Interventions

Acetaminophen 325Mg Tab is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Tylenol for:

• Pain relief
• Fever reduction

Approved in European Union as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Canada as Acetaminophen for:

• Pain relief
• Fever reduction

Approved in Japan as Paracetamol for:

• Pain relief
• Fever reduction

Approved in China as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Switzerland as Paracetamol for:

• Pain relief
• Fever reduction

Who Is Running the Clinical Trial?

Sanford Health

Lead Sponsor

Trials

53

Recruited

2,067,000+

Published Research Related to This Trial

In a study of 64 knee arthroplasty patients, ketoprofen significantly reduced the need for oxycodone pain relief during the first day after surgery, demonstrating its opioid-sparing effect.

After the first day, diclofenac was more effective than placebo in managing pain, while ketoprofen did not show the same level of efficacy beyond the initial postoperative period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the opioid-sparing efficacy of diclofenac and ketoprofen for 3 days after knee arthroplasty. Silvanto, M., Lappi, M., Rosenberg, PH.[2019]

Opioids remain the primary choice for managing postoperative pain, but there is a growing trend towards using non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol, especially with the availability of intravenous forms.

Paracetamol is recommended as the first-line treatment for postoperative pain due to its safety profile, and combining it with opioids and NSAIDs can enhance pain relief while reducing the required dosages and side effects of each medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of postoperative pain]. Dobrogowski, J., Wordliczek, J., Przeklasa-Muszyńska, A., et al.[2013]

Intravenous acetaminophen and ibuprofen are effective options for multimodal postoperative pain management, showing significant opioid-sparing effects and improving patient satisfaction.

While both medications are generally well tolerated and have good safety profiles, the limited number of randomized controlled trials means they should be used cautiously in certain patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous non-opioid analgesia for peri- and postoperative pain management: a scientific review of intravenous acetaminophen and ibuprofen. Koh, W., Nguyen, KP., Jahr, JS.[2022]

Non-opioid analgesics like paracetamol, NSAIDs, and gabapentinoids significantly reduce post-operative morphine requirements, with gabapentinoids showing the highest reduction of ≥13 mg morphine per 24 hours when used alone.

The evidence for the effectiveness of glucocorticoids in reducing opioid use is less convincing, and there is a need for more research on the benefits of combination regimens of these non-opioid drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Dahl, JB., Nielsen, RV., Wetterslev, J., et al.[2022]

NSAIDs are generally more effective than paracetamol for pain relief in dental surgery, while their effectiveness is similar in major and orthopedic surgeries, indicating that the choice of pain management may depend on the type of surgery.

Paracetamol is a safer alternative to NSAIDs due to its lower incidence of adverse effects, making it a preferred option for high-risk patients; combining paracetamol with NSAIDs may enhance pain relief, but more research is needed to assess potential side effects from this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Hyllested, M., Jones, S., Pedersen, JL., et al.[2022]

Paracetamol (1000 mg) is effective for postoperative pain relief, achieving at least 50% pain relief in patients with a number-needed-to-treat (NNT) of 4.6 compared to placebo, based on a review of 40 trials involving 4171 patients.

Combining paracetamol with codeine (60 mg) enhances pain relief, with an NNT of 3.6 for achieving at least 50% pain relief, but this combination may increase the risk of drowsiness and dizziness, indicating a trade-off between efficacy and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain. Moore, A., Collins, S., Carroll, D., et al.[2020]

In a study of 68 adult patients undergoing surgery, intravenous parecoxib provided significantly better pain relief at rest compared to paracetamol, as measured by visual analog scores (VAS).

Both medications were found to be safe with infrequent adverse effects, and overall, patients reported higher satisfaction with pain management in the parecoxib group after 12 hours post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of intravenous paracetamol versus Parecoxib for postoperative analgesia after general anaesthesia. Gupta, K., Rastogi, B., Gupta, PK., et al.[2020]

Multimechanistic approaches to postoperative pain relief, including the use of acetaminophen, can improve pain management, reduce the need for opioids, and lower the risk of opioid-related side effects, enhancing overall surgical outcomes.

Oral acetaminophen, especially when combined with opioids, has been shown to be safe and effective for managing postsurgical pain, and transitioning from intravenous to oral formulations is a reasonable strategy for continued pain control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous multimechanistic postoperative analgesia: a rationale for transitioning from intravenous acetaminophen and opioids to oral formulations. Pergolizzi, JV., Raffa, RB., Tallarida, R., et al.[2013]

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