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?

The purpose of this study is to look at pain management with opioids versus non-opioids after knee arthroscopy. This study will determine 1) whether the most commonly used non-narcotic medications provide pain relief comparable with the most commonly prescribed narcotic medications in patients undergoing arthroscopic knee surgery, and 2) whether patients' characteristics (gender, pre-operative knee symptoms, workers compensation status and employment status) affect pain level following surgery or medication usage.

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).

Is it safe to use opioids and non-opioids like acetaminophen and ibuprofen for postoperative pain after knee surgery?

Acetaminophen (also known as paracetamol) and ibuprofen are generally considered safe for managing postoperative pain, with acetaminophen having a particularly safe profile. Combining these with opioids can reduce the amount of opioids needed, potentially lowering the risk of opioid-related side effects. ^{1 2 3 4 5}

How does the drug acetaminophen and ibuprofen differ from other treatments for postoperative pain after knee surgery?

Acetaminophen and ibuprofen are non-opioid pain relievers that can reduce the need for opioids, which are often used for postoperative pain but can have significant side effects. This combination is part of a multimodal approach to pain management, offering a safer profile and potentially fewer side effects compared to opioid-only treatments. ^{3 4 6 7 8}

What data supports the effectiveness of the drug for postoperative pain after knee surgery?

Research shows that acetaminophen (paracetamol) is effective for treating postsurgical pain and is often used in combination with opioids to enhance pain relief and reduce opioid side effects. Additionally, ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), has been shown to provide significant pain relief, with a lower number of patients needed to treat compared to paracetamol alone. ^{1 3 4 5 6}

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

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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

Continuous multimechanistic postoperative analgesia: a rationale for transitioning from intravenous acetaminophen and opioids to oral formulations. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of the opioid-sparing efficacy of diclofenac and ketoprofen for 3 days after knee arthroplasty. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain. [2020]

4. Poland pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of postoperative pain]. [2013]

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

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. [2022]

6. India pubmed.ncbi.nlm.nih.gov

Clinical evaluation of intravenous paracetamol versus Parecoxib for postoperative analgesia after general anaesthesia. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Intravenous non-opioid analgesia for peri- and postoperative pain management: a scientific review of intravenous acetaminophen and ibuprofen. [2022]