Pain Medication for Postoperative Pain

Recruiting in Palo Alto (17 mi)

Overseen by David Greenberg, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: St. Louis University

Must not be taking: Probenecid, Pentoxifylline

Disqualifiers: Renal impairment, Peptic ulcer, Chemotherapy, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding Toradol, an anti-inflammatory drug, to the usual opioid painkillers can better manage pain after surgery in patients who have had a specific type of bone surgery. These patients are chosen because they don't need the body's natural inflammation process for healing. Toradol works by reducing inflammation, while opioids change how the brain perceives pain. Toradol, also known as ketorolac, is a nonsteroidal anti-inflammatory drug (NSAID) that has been studied for its opioid-sparing effects in postoperative 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.

What data supports the effectiveness of the drugs for postoperative pain?

Research shows that a combination of oxycodone, acetaminophen, and ketorolac can effectively control postoperative pain with fewer complications compared to using opioids alone. Additionally, intravenous acetaminophen and intranasal ketorolac are highlighted as effective components in a multimodal approach to pain management after surgery. ^{1 2 3 4 5}

Is the pain medication safe for humans?

The combination of oxycodone and acetaminophen (Percocet) has been shown to have an improved safety profile with fewer side effects compared to oxycodone alone. Paracetamol (another name for acetaminophen) is also noted for providing effective pain relief with fewer side effects when used in combination with other pain medications. ^{1 2 3 6 7}

How does the drug Hydrocodone/Acetaminophen, Morphine, Oxycodone differ from other drugs for postoperative pain?

This drug combination is unique because it includes both opioids (like Hydrocodone and Morphine) and non-opioid pain relievers (like Acetaminophen), providing a strong pain relief option for severe postoperative pain, but it carries a risk of addiction and side effects, unlike some non-opioid alternatives. ^{8 9 10 11 12}

Research Team

David Greenberg, MD

Principal Investigator

St. Louis University

Eligibility Criteria

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 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Acetaminophen (Analgesic)
• Hydrocodone/Acetaminophen (Opioid Analgesic)
• Ketorolac (Non-Steroidal Anti-Inflammatory Drug)
• Morphine (Opioid Analgesic)
• Oxycodone (Opioid Analgesic)

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.

Participant Groups

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 Canada for the following indications:

Approved in Canada as Hydrocodone/Acetaminophen for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

St. Louis University

Lead Sponsor

Trials

197

Recruited

41,400+

Dr. Laura Simpson

St. Louis University

Chief Medical Officer since 2023

PhD in Molecular and Cellular Biology from Tulane University

Dr. Keith Vendola

St. Louis University

Chief Executive Officer since 2023

PhD in Molecular Biology from Washington University in St. Louis

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

References

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

Efficacy of lornoxicam for acute postoperative pain relief after septoplasty: a comparison with diclofenac, ketoprofen, and dipyrone. [2022]

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

Updates on Multimodal Analgesia for Orthopedic Surgery. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous Oxycodone Versus Other Intravenous Strong Opioids for Acute Postoperative Pain Control: A Systematic Review of Randomized Controlled Trials. [2020]

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

Multi-Modal Pain Control in Ambulatory Hand Surgery. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

[New insights in postoperative pain therapy]. [2006]

6. England 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. [2019]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Postoperative analgesia]. [2013]

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

Effective Postoperative Analgesia Using Intravenous Flurbiprofen and Acetaminophen. [2019]

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

Pain Relief After Operative Treatment of an Extremity Fracture: A Noninferiority Randomized Controlled Trial. [2017]

10. Australia pubmed.ncbi.nlm.nih.gov

Management of postsurgical pain in the community. [2021]

11. South Africa pubmed.ncbi.nlm.nih.gov

Analgesics for pain relief after gynaecological surgery. A two-phase study. [2020]

12. United States 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. [2020]