What side effects are associated with this type of intervention?

Common treatments for pain, such as NSAIDs including ketorolac (Toradol), are associated with several side effects. These include gastrointestinal issues like bleeding and ulcers, renal complications such as reduced glomerular filtration rate and potential acute renal failure, and cardiovascular risks including increased chances of myocardial infarction and other cardiovascular events. Due to these risks, the use of NSAIDs is often limited in duration and monitored closely, especially in patients with pre-existing conditions or those at higher risk for these adverse effects.

What prior FDA approvals exist?

The FDA has approved several drugs for pain management that work by inhibiting COX enzymes, similar to Toradol (ketorolac). Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen are commonly used for their analgesic and anti-inflammatory properties. Additionally, COX-2 selective inhibitors such as celecoxib (Celebrex) have been approved for conditions like osteoarthritis and rheumatoid arthritis due to their targeted action, which aims to reduce gastrointestinal side effects associated with traditional NSAIDs. These drugs are widely used for various types of pain, including post-operative pain, arthritis, and other inflammatory conditions.

What other types of research exist?

Promising novel alternatives to Toradol for pain management include: <ol> <li>Licofelone: A dual lipoxygenase/cyclooxygenase inhibitor showing potential in reducing pain and inflammation.</li> <li></li> </ol> Nitric oxide-donating NSAIDs (e.g., NMI-1093, NMI-1089): These drugs aim to provide pain relief with potentially fewer gastrointestinal side effects. 3. AZD3582: Another investigational drug targeting pain pathways with a focus on reducing inflammation. 4. Disease-modifying osteoarthritis drugs (DMOADs): Although not yet approved, these drugs aim to modify the disease process in osteoarthritis, potentially providing long-term pain relief. 5. Nerve growth factor inhibitors: These are being explored for their ability to target specific pain pathways, offering a new approach to pain management.

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Opioid Analgesic

Pain Medication for Postoperative Pain

Phase 3

Recruiting

Led By David Greenberg, MD

Research Sponsored by St. Louis University

Eligibility Criteria Checklist

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

Must have

Femoral Shaft or Neck bone lesion

18 years old or greater

Must not have

History of Peptic Ulcer Disease

History of heart failure or cardiovascular disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to six weeks post-op

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include risk of bleeding from Toradol (an NSAID), stomach ulcers, kidney problems; and from opioids: drowsiness, constipation, nausea/vomiting and potential dependency issues.

Eligibility Criteria

Inclusion Criteria

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

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I have a bone lesion in my femur.

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I am 18 years old or older.

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

Exclusion Criteria

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

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I have had peptic ulcer disease in the past.

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I have a history of heart failure or heart disease.

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I have had heart bypass surgery.

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I am on chemotherapy that doesn't allow for NSAID use.

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I have a fracture caused by my cancer.

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I cannot use toradol due to my liver condition.

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I am currently taking the medication probenecid.

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I have had severe kidney problems in the past.

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I have a blood clotting disorder or need blood-thinning medication during the study.

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I am currently taking Pentoxifylline.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to six weeks post-op

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to six weeks post-op

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to six weeks post-op for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Milligram Morphine Equivalent (MME) of Opioid Medications Utilized

Secondary study objectives

Numerical Rating Scale (NRS)

Patient Reported Outcomes Measurement System (PROMIS) Pain Intensity Scale

Single Assessment Numerical Evaluation (SANE)

Awards & Highlights

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Experimental ArmExperimental Treatment6 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: ControlPlacebo Group6 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Oxycodone Acetaminophen

2017

Completed Phase 3

~180

Hydrocodone/Acetaminophen

2020

Completed Phase 4

~300

Ketorolac

2014

Completed Phase 4

~1760

Morphine

2013

Completed Phase 4

~2230

Acetaminophen

2017

Completed Phase 4

~2030

Oxycodone

2014

Completed Phase 4

~2210

0 / 13Eligibility 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

Nonsteroidal anti-inflammatory drugs (NSAIDs) like Toradol (ketorolac) work by inhibiting cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are crucial in the biosynthesis of prostaglandins, which are lipid compounds that mediate inflammation, pain, and fever. By blocking COX enzymes, NSAIDs reduce the production of prostaglandins, thereby alleviating pain and inflammation. This mechanism is particularly important for pain patients as it provides a non-opioid option for pain relief, potentially reducing the risk of opioid dependency and associated side effects. Understanding this mechanism helps in selecting appropriate pain management strategies tailored to individual patient needs and comorbidities.

Central Nervous System Targets: Supraspinal Mechanisms of Analgesia.Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence.The Role of Descending Modulation in Manual Therapy and Its Analgesic Implications: A Narrative Review.