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

Trial Summary

What is the purpose of this trial?

To determine is low-dose ketorolac use in the early post-operative period (within 48 hours) provides adequate analgesia without long term adverse effect on spinal fusion rates when compared to post-operative analgesia without the use of NSAIDs.

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 data supports the effectiveness of the drug Ketorolac for post-surgical pain in thoracolumbar fusion?

Research shows that Ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), can effectively reduce postoperative pain and decrease the need for opioids after surgeries, including thoracolumbar spinal fusions. It has been found to provide pain relief comparable to morphine, making it a useful alternative for managing acute postoperative pain. ^{1 2 3 4 5}

Is ketorolac generally safe for use in humans?

Ketorolac is generally considered safe for short-term use in managing postoperative pain, but it may increase the risk of bleeding and inhibit bone healing in some cases. It is important to monitor for these potential side effects, especially in surgeries where bleeding is a concern. ^{1 2 3 6 7}

How is the drug ketorolac unique for post-surgical pain in thoracolumbar fusion?

Ketorolac is unique because it is the only nonsteroidal anti-inflammatory drug (NSAID) available in the U.S. that can be given intramuscularly for pain relief, offering an alternative to opioids without binding to opioid receptors. It effectively reduces the need for opioids, which is important given the opioid addiction crisis. ^{1 2 3 4 6}

Research Team

Doris Tong, MD

Principal Investigator

Michigan Spine and Brain Surgeons

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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 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]

References

1. Netherlands 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. [2022]

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

Use of ketorolac tromethamine in children undergoing scoliosis surgery. an analysis of complications. [2019]

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

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. [2013]

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

The use of ketorolac in the management of postoperative pain. [2022]

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

The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. [2019]

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

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? [2021]

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

Intracranial hemorrhage requiring surgery in neurosurgical patients given ketorolac: a case-control study within a cohort (2001-2010). [2022]