Ketorolac for Post-Surgical Pain in Thoracolumbar Fusion

Overseen By Doris Tong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ascension South East Michigan

Must not be taking: Antipsychotics, Antidepressants, Chemotherapy

Disqualifiers: Smoking, Rheumatological, Psychiatric, Cardiovascular, 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: Unknown

Duration: 48 hours

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the pain reliever ketorolac can effectively manage pain after spine surgery without hindering the healing process. It compares ketorolac to a placebo (a harmless substance with no therapeutic effect) to determine which provides better pain relief. Individuals who have undergone minimally invasive spine surgery on three or fewer levels and do not smoke might be suitable candidates. The goal is to find a safe method to reduce post-surgical pain without affecting the spine's healing. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on major anti-psychotic or anti-depressant medications, chemotherapeutic agents, or have a history of systemic steroid use, you may not be eligible to participate.

What is the safety track record for ketorolac?

Research has shown that ketorolac is generally safe for managing pain after surgery. Studies have found that it can effectively reduce the need for strong painkillers like opioids without causing additional pain. This makes ketorolac a viable option for managing pain after surgeries such as spinal fusion, where avoiding interference with healing is crucial.

One study found that ketorolac did not affect the healing of spinal fusions, addressing a major concern for patients undergoing spine surgery. Another study showed that ketorolac provides significant pain relief, particularly in the first six hours after surgery, when patients often need it most.

Overall, ketorolac appears to be well-tolerated, with no major side effects reported in these studies. This suggests that using ketorolac for short-term pain relief after spine surgery could be a safe option for many patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for post-surgical pain in thoracolumbar fusion rely on opioids or other common analgesics, which can have significant side effects and addiction potential. Ketorolac stands out because it is a nonsteroidal anti-inflammatory drug (NSAID) that provides pain relief without the risk of addiction associated with opioids. Unlike other options, Ketorolac is administered intravenously, which can offer rapid pain relief, making it particularly appealing for managing post-surgical pain effectively. Researchers are excited about Ketorolac as it could potentially reduce reliance on opioids, leading to safer pain management strategies following surgery.

What is the effectiveness track record for ketorolac in managing post-surgical pain?

Research shows that ketorolac, which participants in this trial may receive, effectively manages post-surgical pain. It reduces the need for opioids, strong painkillers with potential side effects. Studies have found that ketorolac offers good pain relief after spinal surgery with minimal side effects. When administered in small doses soon after surgery, it does not interfere with spinal fusion, the spine's healing process. Ketorolac is considered a strong option for pain control after lumbar spinal fusion surgery. Participants in this trial will receive either ketorolac or a placebo to evaluate its effectiveness in this context. ^{1 2 5 6 7}

Who Is on the Research Team?

Doris Tong, MD

Principal Investigator

Michigan Spine and Brain Surgeons

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need a specific back surgery (thoracolumbar posterior lumbar instrumented interbody fusion) using minimally invasive techniques and a certain bone protein. Smokers, those with recent surgeries at the same spot, chronic inflammatory conditions, steroid use in past 3 months, or major psychiatric illnesses can't join.

Inclusion Criteria

Consent to study participation

I am using BMP for spinal fusion at a dose of 1.05mg per level or less.

I am over 18 years old.

Exclusion Criteria

I have a long-term inflammatory or rheumatological condition.

Current creatinine > 1.5mg/dl

My surgery is due to injury-related damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose ketorolac or placebo for analgesia in the early post-operative period (within 48 hours)

48 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness, including fusion construct evaluation and quality of life assessments

24 months

Regular follow-up visits, including face-to-face interviews

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac

Trial Overview The study tests if low-dose ketorolac given within the first 48 hours after spine surgery provides good pain relief without affecting long-term success of spinal fusions compared to standard painkillers that don't include NSAIDs like ketorolac.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Ketorolac 15 mg (15mg/ml) IV Q6H

Group II: Placebo Placebo Group 1 Intervention

Drug: Placebo Saline 1 ml IV Q6H

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?

Ascension South East Michigan

Lead Sponsor

Trials

19

Recruited

32,400+

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Published Research Related to This Trial

In a study of 4086 patients undergoing elective neurosurgery, those who received ketorolac had a significantly lower incidence of symptomatic intracranial hemorrhage (ICH) at 0.5% compared to 1.3% in those who did not receive the drug, suggesting a potential protective effect against bleeding.

Despite the lower observed risk of ICH in patients taking ketorolac, the adjusted odds ratio was close to 1, indicating that the findings may not be conclusive enough to definitively establish the safety of ketorolac in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial hemorrhage requiring surgery in neurosurgical patients given ketorolac: a case-control study within a cohort (2001-2010). Magni, G., La Rosa, I., Melillo, G., et al.[2022]

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory drug (NSAID) for managing moderate to severe postoperative pain, reducing the need for opioid analgesics, which can help minimize opioid-related side effects.

Administered intramuscularly, ketorolac reaches peak plasma levels in about 45 to 50 minutes and has a low incidence of side effects, making it a promising option for both inpatient and outpatient pain management, although further research is needed to fully understand its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. Lassen, K., Epstein-Stiles, M., Olsson, GL.[2013]

In a study of 225 patients undergoing thoracolumbar spinal fusions, a single dose of intraoperative IM ketorolac did not significantly reduce overall opioid use or length of hospital stay, indicating it may not be effective in minimizing opioid requirements post-surgery.

However, ketorolac showed potential benefits in early pain control on the first postoperative day, suggesting it could be a useful component of a multimodal pain management strategy in spine surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Intraoperative Local Ketorolac on Opioid Use in the Management of Postoperative Pain in Thoracolumbar Spinal Fusions: A Retrospective Cohort Study. Lytle, E., Claus, C., Yoon, E., et al.[2022]

In a study involving 176 postoperative patients, ketorolac (10 mg orally) provided analgesic efficacy comparable to both 5 mg and 10 mg doses of morphine, significantly outperforming placebo.

Ketorolac is a safe and effective option for managing acute postoperative pain, serving as a non-opioid alternative to traditional opioid therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ketorolac in the management of postoperative pain. DeAndrade, JR., Maslanka, M., Maneatis, T., et al.[2022]

In a retrospective study of breast surgery patients over three years, ketorolac did not significantly increase the risk of postoperative hematoma formation, with rates of 3.5% in those receiving ketorolac compared to 2.5% in those who did not.

The overall hematoma rate for the entire cohort was 2.8%, suggesting that ketorolac can be safely used for postoperative pain control without raising concerns about bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? Nguyen, BN., Barta, RJ., Stewart, CE., et al.[2021]

In a study of 208 children who underwent scoliosis surgery, the use of ketorolac did not lead to a significant increase in postoperative complications such as transfusion or reoperation rates.

The analysis showed no significant differences in various clinical factors between children who received ketorolac and those who did not, suggesting that ketorolac can be safely used in this surgical context without raising complication risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketorolac tromethamine in children undergoing scoliosis surgery. an analysis of complications. Vitale, MG., Choe, JC., Hwang, MW., et al.[2019]

A study of 288 patients who underwent spinal fusion found that postoperative administration of ketorolac significantly increased the rate of nonunion, with 29 cases in the ketorolac group compared to only 5 in the non-drug group.

The research indicates that ketorolac, a common nonsteroidal anti-inflammatory drug, adversely affects spinal fusion rates, suggesting it should be avoided in the early postoperative period to enhance healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Glassman, SD., Rose, SM., Dimar, JR., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11536961/

The efficacy and safety of ketorolac for postoperative pain ... The findings suggest that Ketorolac effectively reduces pain and opioid use postoperatively, supporting its role in multimodal analgesia for lumbar spinal ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6347897/

The effect of ketorolac on posterior thoracolumbar spinal ... Ketorolac has been shown to provide quality postoperative pain control and decrease opioid requirement with minimal side effects following spinal surgery.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1529943021008962

The effect of ketorolac on posterior minimally invasive ... Short-term use of low-dose ketorolac in patients who have undergone MIS TLIF with BMP demonstrated noninferior fusion rates.

4. ircmj.com ircmj.com/article_224575_bdb2c936f58ed4f751297007a4408a7f.pdf

Comparing Ketorolac and Ketamine for Postoperative Pain ... →Meaning Ketorolac or ketamine with morphine improves pain control after lumbar fusion, with ketorolac being most effective. Comparing Ketorolac ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02700451

Post-op Acetaminophen vs NSAID Use on Lumbar Spinal ... A randomized controlled trial of post-operative acetaminophen versus nonsteroidal anti-inflammatory drug (NSAID) use on lumbar spinal fusion outcomes.

6. ircmj.com ircmj.com/article_200782_964d04b3cd5a8f28a6c0156b4822ba4d.pdf

Efficacy and Safety of Ketorolac in the Treatment ... Findings The study found that ketorolac did not significantly reduce postoperative VAS scores compared to control groups,.

7. bmjopen.bmj.com bmjopen.bmj.com/content/9/1/e025855

The effect of ketorolac on posterior thoracolumbar spinal ... Our goal is to demonstrate that ketorolac is a safe and effective adjuvant for postoperative analgesia without any adverse effect on fusion rates in adults.