Pain Medication for Postoperative Pain

Recruiting at 1 trial location

Overseen By Allison Gruender, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: St. Louis University

Must not be taking: Probenecid, Pentoxifylline

Disqualifiers: Renal impairment, Peptic ulcer, Chemotherapy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a pain relief strategy using both NSAIDs (a type of non-opioid painkiller) and opioids compared to using only opioids after certain bone surgeries. It targets individuals undergoing surgery to place a rod in the thigh bone (femur) without a fracture, allowing safe use of NSAIDs. Participants should have a bone lesion in the femur but not an active fracture. The trial will compare two groups: one receiving a combination of pain treatments including NSAIDs, and another receiving only opioids (such as Hydrocodone/Acetaminophen, Morphine, or Oxycodone). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in pain management.

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 currently using probenecid or pentoxifylline, or if you have certain medical conditions that prevent NSAID or toradol use.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketorolac is generally safe for healthy individuals and effectively relieves pain immediately after surgery. Studies have found that taking multiple doses over a short period does not increase side effects compared to a placebo, indicating ketorolac is well-tolerated in the short term.

In this trial, the opioid treatments include hydrocodone-acetaminophen and oxycodone, both safely used for moderate to severe post-surgical pain. A single dose of oxycodone effectively relieves pain. Morphine is also a common pain treatment, but it requires careful use, especially in individuals with kidney problems, to prevent drowsiness or breathing issues.

Since this trial is in Phase 3, evidence already supports the safety of these treatments. Phase 3 trials indicate that the treatments have undergone prior safety testing in humans. Overall, these medications are widely used and have been shown to be safe for many patients when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for postoperative pain?

Researchers are excited about this trial because it explores the potential benefits of using IV ketorolac as an experimental option for managing postoperative pain. Unlike standard treatments that primarily rely on opioids like hydrocodone, oxycodone, and morphine, IV ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that offers pain relief without the same level of opioid-related side effects and risks such as addiction. This trial also investigates tailored dosing based on age and renal function, potentially leading to more personalized and safer pain management strategies. By reducing reliance on opioids, this approach could significantly improve recovery experiences for patients after surgery.

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

Research shows that ketorolac, a type of pain reliever, effectively reduces pain after surgery. In this trial, participants in the experimental arm will receive ketorolac, which studies have shown helps lessen pain and reduce the need for stronger painkillers like morphine. For instance, one study found that patients using ketorolac experienced significantly less pain over a 12-24 hour period. This suggests that ketorolac can play an important role in managing post-surgical pain. While some studies have mixed results, many support its role in reducing opioid use and effectively managing pain. ^{6 7 8 9 10}

Who Is on the Research Team?

David Greenberg, MD

Principal Investigator

St. Louis University

Are You a Good Fit for This Trial?

This trial is for adults planning to undergo prophylactic intramedullary nailing of the femur due to bone lesions. It's not suitable for those with coagulation disorders, current fractures, severe kidney or liver disease, peptic ulcer disease, certain heart conditions, allergies to acetaminophen or NSAIDs, opioid addiction or dependence, pregnancy, and those on specific medications like probenecid.

Inclusion Criteria

I have a bone lesion in my femur.

I am planning to have surgery to prevent fractures in my thigh bone.

Exclusion Criteria

You have a history of depending too much on or misusing opioid medications.

You are allergic to opioids and cannot use them.

You are allergic to acetaminophen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive post-op pain management with either ketorolac and opioids or opioids alone following prophylactic intramedullary nailing of the femur

2 weeks

Daily monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain and functional assessments

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen
• Hydrocodone/Acetaminophen
• Ketorolac
• Morphine
• Oxycodone

Trial Overview The study investigates the effectiveness of using a pain reliever called Toradol in combination with opioids versus just opioids alone after surgery for securing weak bones in patients without fractures. The goal is to see if adding an NSAID can help manage post-op pain without affecting healing.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 6 Interventions

For the first 24 hours following surgery, patients younger than 65 years old will be administered a maximum of 120 mg/day bolus IV ketorolac (30 mg every 6 hours). Patients older than 65 years old or with history of advanced renal impairment will receive a maximum of 60 mg/day bolus IV ketorolac (15 mg every 6 hours). All patients may also be given acetaminophen 500 mg PO Q4 hours PRN for mild pain, oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate- severe pain, and morphine IV PRN (or other opioid) for severe breakthrough pain while hospitalized. At discharge, they will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours, quantity 50. Those with preexisting liver disease will be prescribed the equivalent in oxycodone and will not receive acetaminophen for mild pain.

Group II: Control Placebo Group 6 Interventions

Following surgery, patients will be given acetaminophen 500 mg PO Q4 hours PRN for mild pain, oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate-severe pain, and morphine IV PRN (or other opioid) for severe breakthrough pain while hospitalized. They will also be given a placebo injection of normal saline every 6 hours for the first 24 hours following surgery. At discharge, patients will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours PRN quantity 50, unless they have preexisting liver disease, in which case they will be prescribed the equivalent in oxycodone. They will not receive a nerve block.

Hydrocodone/Acetaminophen is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Vicodin for:

• Moderate to severe pain

Approved in Canada as Hydrocodone/Acetaminophen for:

• Moderate to severe pain

Approved in European Union as Hydrocodone/Acetaminophen for:

• Moderate pain

Who Is Running the Clinical Trial?

St. Louis University

Lead Sponsor

Trials

197

Recruited

41,400+

Published Research Related to This Trial

In a study of 53 patients who underwent surgery on the infrarenal aorta and large vessels, various combinations of nonopioid drugs were tested for postoperative pain relief, all showing effective analgesic results.

The combination of paracetamol with tramadol not only provided faster pain relief but also reduced the need for tramadol, making it a safer option for patients at higher risk of ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Postoperative analgesia]. Kazennov, VV., Shishkin, MN., Amerov, DB., et al.[2013]

In a study involving 200 patients undergoing elective septoplasty, lornoxicam was found to be effective in managing acute postoperative pain, but its efficacy was not superior to that of other nonopioid analgesics like diclofenac, ketoprofen, and dipyrone.

Patients receiving placebo required significantly more additional analgesia (pethidine) compared to those receiving active treatments, indicating that all active medications provided better pain relief than placebo, with no significant differences in adverse effects among the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of lornoxicam for acute postoperative pain relief after septoplasty: a comparison with diclofenac, ketoprofen, and dipyrone. Sener, M., Yilmazer, C., Yilmaz, I., et al.[2022]

In a study of 79 patients undergoing thumb carpometacarpal arthroplasty or distal radius ORIF, the combination of oxycodone, acetaminophen, and ketorolac showed a trend towards better postoperative pain control and reduced opioid usage compared to other regimens.

Although not statistically significant, the group receiving oxycodone, acetaminophen, and ketorolac experienced fewer complications, suggesting that this combination may enhance safety and efficacy in managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-Modal Pain Control in Ambulatory Hand Surgery. Harrison, RK., DiMeo, T., Klinefelter, RD., et al.[2018]

In a study involving patients aged 24 to 54 undergoing dental surgery, acetaminophen combined with an NSAID (flurbiprofen) resulted in a significantly shorter recovery time compared to the combination of fentanyl and NSAID, indicating a quicker discharge from the operating room.

Despite the difference in recovery times, both analgesic combinations provided similar pain relief, suggesting that acetaminophen can effectively replace fentanyl in managing postoperative pain when narcotics are not suitable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Postoperative Analgesia Using Intravenous Flurbiprofen and Acetaminophen. Yoshida, M., Shimizu, Y., Yoshida, K., et al.[2019]

In a study of 52 patients recovering from extremity fracture surgery, acetaminophen alone was found to be noninferior to a combination of acetaminophen and tramadol for pain relief, with similar satisfaction scores (8.3 vs. 8.5).

Given that tramadol can have more side effects and potential for addiction, the findings support using acetaminophen as the primary pain management option after such surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain Relief After Operative Treatment of an Extremity Fracture: A Noninferiority Randomized Controlled Trial. Helmerhorst, GTT., Zwiers, R., Ring, D., et al.[2017]

Postoperative opioid use for pain management can lead to addiction and prolonged recovery, as seen in a patient who experienced severe withdrawal after knee surgery 10 years ago.

In contrast, using a combination of anti-inflammatory medications (meloxicam, high-dose acetaminophen, and topical diclofenac) after a second knee surgery resulted in excellent pain control and a rapid recovery, suggesting that opioids may not be necessary for most patients after arthroplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Tale of Two Knee Implants in the Same Person: Narcotics for the First and Anti-inflammatory Drugs for the Second. Stevenson, DD., Gasko, JL.[2020]

Intravenous oxycodone was found to be more effective for managing acute postoperative pain compared to fentanyl and sufentanil, and it showed similar efficacy to morphine, based on a systematic review of 11 studies involving adult patients.

While oxycodone had a tendency for more side effects than fentanyl, its side effect profile was comparable to that of morphine and sufentanil, and patient satisfaction was generally higher with oxycodone compared to sufentanil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Oxycodone Versus Other Intravenous Strong Opioids for Acute Postoperative Pain Control: A Systematic Review of Randomized Controlled Trials. Raff, M., Belbachir, A., El-Tallawy, S., et al.[2020]

Oral analgesics containing paracetamol, caffeine, codeine, and meprobamate, as well as dipyrone with pitofenone and fenpiverinium, provided satisfactory pain relief when administered 12 hours post-surgery in uncomplicated cases.

Parenteral administration of pethidine and dipyrone was ineffective for pain relief, suggesting a need to reconsider their use in postoperative care, while side effects from the medications were generally mild and infrequent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesics for pain relief after gynaecological surgery. A two-phase study. Bloch, B., Smythe, E., Weeks, R.[2020]

Effective pain management after surgery involves pre-discharge discussions about expected pain and a clear management plan, with paracetamol and non-steroidal anti-inflammatory drugs being suitable for most patients.

While short-acting opioids can be used for a limited time post-surgery, they must be carefully monitored due to the risk of adverse effects and misuse, and gabapentinoids are primarily effective for neuropathic pain rather than nociceptive pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of postsurgical pain in the community. MacPherson, R., Pattullo, G.[2021]

A multimodal approach to pain control after orthopedic surgery, which includes nonopioid agents like intravenous acetaminophen and intranasal ketorolac, offers better pain relief with fewer side effects compared to using opioids alone.

This review highlights the importance of incorporating newer nonopioid medications alongside established treatments like ketamine and gabapentinoids to enhance analgesia, especially in the context of the ongoing opioid epidemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates on Multimodal Analgesia for Orthopedic Surgery. Pitchon, DN., Dayan, AC., Schwenk, ES., et al.[2018]

Postoperative therapy with NSAIDs after tonsillectomy may lead to a higher rate of reoperations, suggesting that their use should be approached with caution.

COX-2 inhibitors combined with intravenous opioids enhance recovery and functional outcomes after knee replacement surgery, indicating a beneficial approach for pain management in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New insights in postoperative pain therapy]. Brack, A., Böttiger, BW., Schäfer, M.[2006]

The new oxycodone 10-mg/acetaminophen 325-mg formulation (Percocet) was found to be more effective than a higher dose of oxycodone alone in managing acute pain after oral surgery, based on a study of 141 patients.

This combination not only provided faster pain relief but also resulted in fewer treatment-related side effects, highlighting its potential as a safer alternative for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. Gammaitoni, AR., Galer, BS., Bulloch, S., et al.[2019]

Citations

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The efficacy and safety of ketorolac for postoperative pain ... In the 12-24-h period, Ketorolac continued to show significant pain reduction (MD = - 0.48; 95% CI: - 0.68 to - 0.28; P < 0.0001), but this ...

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Peri-Operative Pain Management MD Anderson offers three coordinated pain specialty core services, consisting of Acute Pain Medicine, Chronic Pain Medicine, and Supportive Care. Guidelines for ...

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Pain medicines after surgery Pain medicines and anesthesia can control pain after surgery and lead to faster healing.

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Safe and Effective Pain Control After Surgery for Children ... Information on how to provide safe and effective pain control after surgery for children and teens .

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CDC Clinical Practice Guideline for Prescribing Opioids ... This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years.