Low-Dose Ketorolac for Multiple Trauma

Recruiting at 1 trial location

Overseen By Adam N Musick, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must not be taking: Steroids, Immune-modulating drugs, Opioids, NSAIDs

Disqualifiers: Pregnancy, Renal disease, Heart disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 5 days

458 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a low-dose NSAID, ketorolac, can reduce long-term opioid use in patients with multiple traumatic injuries requiring surgery. The researchers aim to determine if taking ketorolac during the first five days in the hospital manages pain more effectively than a placebo, leading to reduced opioid need and improved pain response. Ideal participants are those hospitalized for severe musculoskeletal trauma requiring surgery, with an expected hospital stay of at least five days. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how ketorolac can benefit more patients in real-world settings.

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 require a daily NSAID or aspirin regimen, except for low-dose aspirin (81 mg).

What is the safety track record for ketorolac?

Research has shown that ketorolac, a type of pain reliever, is generally safe for adults, though some risks exist. Studies indicate that taking multiple doses of oral ketorolac increases the chance of side effects by about 39% compared to a placebo. Serious side effects are rare but can include bleeding or a collection of blood outside blood vessels at the surgery site. In one study, 1.5% of patients using a specific form of ketorolac experienced these serious issues. Overall, ketorolac is well-tolerated and often used for managing moderate to severe pain. However, as with any medication, it's important to consider the benefits and potential risks. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard care for managing pain in multiple trauma, which typically involves opioids and other analgesics, ketorolac offers a non-opioid alternative that can help reduce reliance on narcotics. Researchers are excited about ketorolac because it is a nonsteroidal anti-inflammatory drug (NSAID) that works by reducing hormones that cause inflammation and pain. This makes it particularly appealing as it provides effective pain relief without the addictive potential of opioids, potentially leading to fewer side effects and complications associated with long-term opioid use. Additionally, ketorolac is administered intravenously, which allows for rapid relief, a crucial factor in acute trauma care.

What evidence suggests that low-dose ketorolac might be an effective treatment for reducing chronic opioid use in multiple trauma patients?

Studies have shown that ketorolac effectively relieves pain, especially post-surgery. It works well with opioids to significantly reduce both pain and the need for additional opioids. In this trial, one treatment arm will receive low-dose ketorolac alongside standard of care (SOC) multimodal analgesia. Research indicates that ketorolac use in trauma patients can shorten hospital stays, decrease opioid use, and improve pain management. For those with bone or joint injuries, ketorolac has been linked to less pain and reduced opioid use, making it a promising option for managing pain without heavily relying on opioids. ^{3 4 6 7 8}

Who Is on the Research Team?

Arun Aneja, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for orthopaedic polytrauma patients with multiple injuries who may be at risk of developing chronic opioid use. Participants must not have conditions that prevent NSAID use, such as certain bleeding disorders, kidney failure, or known allergies to ketorolac.

Inclusion Criteria

I had a severe injury needing surgery.

Patients who can be followed at our facility for at least 6 months

I expect to be in the hospital for 5 days or more.

Exclusion Criteria

My injury occurred over 24 hours ago.

I am at risk of severe bleeding or have experienced hemorrhagic shock.

I have had a heart attack, stroke, or a bleeding disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive 15 mg of intravenous ketorolac or placebo every 6 hours during the first five hospital days, in addition to standard of care multimodal analgesia

5 days

Daily monitoring during hospital stay

Follow-up

Participants are monitored for opioid use and functional response to pain at discharge, 2 weeks, 6 weeks, 3 months, and 6 months post-injury

6 months

Visits at discharge, 2 weeks, 6 weeks, 3 months, and 6 months

Long-term Follow-up

Participants' chronic opioid use is assessed at 6 months post-injury

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac

Trial Overview The study tests if low-dose ketorolac injections can reduce long-term opioid dependency compared to a saline placebo in trauma patients. It measures pain and opioid consumption over five days and follows up on pain function and opioid use up to six months post-injury.

How Is the Trial Designed?

Group I: Standard of Care (SOC) + Ketorolac Experimental Treatment 1 Intervention

The treatment arm will receive 15 mg of intravenous (IV) ketorolac every 6 hours during the first five hospital days, in addition to standard of care (SOC) multimodal analgesia according to each site's institutional protocol.

Group II: Standard of Care (SOC) Placebo Group 1 Intervention

The placebo arm will receive 2 mL of intravenous (IV) saline every 6 hours during the first five hospital days, in addition to standard of care (SOC) multimodal analgesia according to each site's institutional protocol.

Ketorolac is already approved in United States, European Union, Switzerland for the following indications:

Approved in United States as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea
• Idiopathic pericarditis
• Ocular itching

Approved in European Union as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea

Approved in United States as Acular for:

• Ocular itching
• Inflammation after eye surgery

Approved in United States as Sprix for:

• Moderate to severe pain

Approved in Switzerland as Ketorolac for:

• Moderate to severe pain
• Postoperative pain

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK545172/

Ketorolac - StatPearls - NCBI Bookshelf Widely employed in postoperative scenarios for pain control, ketorolac is particularly effective when combined with opioids, leading to a significant reduction ...

2. sprix.com sprix.com/clinical-data

SPRIX® | Clinical Data In clinical studies, 1.5% of patients treated with SPRIX experienced serious adverse events of bleeding or hematoma at the operative site vs 0.4% treated with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03671746

Inflammatory Markers in Trauma Patient Outcomes Preliminary data has shown: (1) elevated blood cytokine concentrations during the acute phase of trauma are correlated with the development of fatal post- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4918732/

Double-blind, randomized, double-dummy clinical trial ... The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity.

5. med.uvm.edu med.uvm.edu/docs/jc_trauma_jan_2024/orthopaedics-documents/jc_trauma_jan_2024.pdf?sfvrsn=8464b9ac_0

Low-Dose Short-Term Scheduled Ketorolac Reduces ... ketorolac is associated with reduced length of stay, opioid use, and pain in orthopaedic polytrauma patients. Design: Double-blinded, randomized controlled ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11584978/

Evidence‐based safety profile of oral ketorolac in adults In summary, multiple intakes of oral ketorolac increase the risk of any adverse event by 39.16% compared to a placebo; however, this effect is ...

7. clinicaltrials.gov clinicaltrials.gov/ct2/keydates/NCT01351090

Study of the Safety, Tolerability and Analgesic Efficacy ... Study of the Safety, Tolerability and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine (IN) for Postoperative Pain. ClinicalTrials.gov ID ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01471639

An Efficacy and Safety Trial of Intranasal Ketorolac in ... The purpose of this study is to determine the effectiveness, the safety, and the tolerability of intranasal ketorolac (Sprix) in relieving acute pain in adults ...