Ketorolac for Pain Management

(KETOROLAC-ICU Trial)

Overseen By Vincent I Lau, MD MSc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Alberta

Must be taking: Stress ulcer prophylaxis

Must not be taking: ACE inhibitors, ARBs, NSAIDs, Probenecid

Disqualifiers: Chronic kidney disease, GI bleeding, Heart disease, Liver impairment, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 28

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if ketorolac, a type of painkiller, can safely reduce the need for opiates in critically ill ICU patients. The goal is to manage pain effectively without heavy reliance on opiates, which can lead to dependence. Suitable candidates for this trial are ICU patients experiencing pain that affects their comfort and daily care. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking pain management solutions.

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 certain medications like ACE inhibitors, ARBs, or NSAIDs for other reasons. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that ketorolac is likely to be safe for humans?

Research shows that ketorolac, a type of pain reliever, usually works well. Some studies have examined its safety. One study found no increase in heart, stomach, or kidney problems with a single use. However, other research has noted some risks, such as stomach issues, kidney problems, and bleeding.

Ketorolac is already approved for treating pain in other situations, indicating prior safety testing. Since it is now being tested in very sick patients, monitoring for side effects is crucial. These patients receive close monitoring to manage any potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ketorolac is unique because it offers a potent, non-opioid option for pain management, which is especially appealing given the current dependency on opioids and traditional NSAIDs like ibuprofen and naproxen. Unlike other treatments, ketorolac is particularly effective for short-term pain relief and can help minimize the need for opioid use, reducing the risk of addiction. Researchers are excited about ketorolac because it targets pain through a different mechanism, specifically inhibiting the cyclooxygenase enzymes, which play a key role in pain and inflammation, potentially providing rapid relief with a good safety profile.

What evidence suggests that ketorolac might be an effective treatment for pain management in critically ill patients?

Research has shown that ketorolac, which participants in this trial may receive, effectively reduces pain and lessens the need for opioids after surgery. In several studies, patients who took ketorolac required fewer opioids to manage their pain. This is important because it can lower the risk of opioid addiction. Ketorolac blocks certain enzymes that cause pain and swelling, making it a valuable option for managing pain and reducing opioid use. ^{5 6 7 8 9}

Who Is on the Research Team?

Vincent I Lau, MD MSc

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for critically ill ICU patients who need pain management. It's exploring if lower doses of Ketorolac, an NSAID, can reduce the need for opiates. Patients with risks of GI bleeding or kidney injury are typically excluded but may be monitored closely in this study.

Inclusion Criteria

I have been admitted to the ICU.

I experience pain that scores more than 1 on a pain scale.

I am older than 18 years.

Exclusion Criteria

I am currently taking ACE inhibitors or ARBs in the ICU.

I have an active stomach or duodenal ulcer.

Participants expected to stay in ICU < 48 hours

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either ketorolac or placebo along with standard care in the ICU

4 weeks

Daily monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Regular assessments at Days 28 and 90

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac

Trial Overview

The study tests whether Ketorolac at low doses is a safe and effective alternative to opiates for pain control in ICU patients. Participants will either receive Ketorolac or a placebo to assess the feasibility of using NSAIDs over opiates.

How Is the Trial Designed?

Group I: Ketorolac Experimental Treatment 1 Intervention

Ketorolac administration + standard of care. Participants will not be allowed to have co-administered alternative NSAIDs during the duration of their exposure on the study drug. After each administered dose, overall analgesic requirements should be assessed by the treating team (as per local institutional guidelines and practices), with attempts to wean analgesic infusions or use reduced doses of analgesic medications (especially if objective pain score measures are zero, e.g. CPOT or NRS/VAS).

Group II: Placebo Placebo Group 1 Intervention

Placebo administration + standard of care. Participants will not be allowed to have co-administered alternative NSAIDs during the duration of their exposure on the study drug. After each administered dose, overall analgesic requirements should be assessed by the treating team (as per local institutional guidelines and practices), with attempts to wean analgesic infusions or use reduced doses of analgesic medications (especially if objective pain score measures are zero, e.g. CPOT or NRS/VAS).

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

A single dose of systemic ketorolac (60 mg) significantly reduces early postoperative pain and opioid consumption, making it an effective adjunct for pain management in surgical patients, based on a systematic review of 13 trials involving 782 subjects.

The 60 mg dose of ketorolac also decreases the incidence of postoperative nausea and vomiting, enhancing its safety profile compared to lower doses, which did not show significant benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. De Oliveira, GS., Agarwal, D., Benzon, HT.[2022]

In a study involving 70 infants and children who underwent congenital heart surgery, ketorolac was found to effectively manage postoperative pain without increasing the risk of bleeding complications compared to opioid analgesics alone.

The results showed that patients receiving ketorolac had lower median chest-tube drainage and no significant wound bleeding, indicating its safety and efficacy as a pain management option in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized trial of ketorolac after congenital heart surgery. Gupta, A., Daggett, C., Drant, S., et al.[2019]

Ketorolac can cause serious side effects like gastrointestinal bleeding and renal impairment, but the risk of these events has decreased since dosage guidelines were revised, making it slightly safer than opioids for pain management.

The risk of adverse effects increases with higher doses, prolonged use beyond 5 days, or in vulnerable populations such as the elderly, highlighting the importance of careful patient selection and adherence to prescribing guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimising the adverse effects of ketorolac. Reinhart, DI.[2018]

A significant portion of ketorolac use in Italy is off-label, with 553 out of 822 reported cases of suspected adverse drug reactions (ADRs) classified as off-label, indicating a widespread practice that raises safety concerns.

Off-label use of ketorolac is associated with a higher incidence of serious ADRs (58.6%) compared to on-label use (39.0%), particularly gastrointestinal events, highlighting the need for careful monitoring and regulation by health authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions associated with off-label use of ketorolac, with particular focus on elderly patients. An analysis of the Italian pharmacovigilance database and a population based study. Viola, E., Trifirò, G., Ingrasciotta, Y., et al.[2018]

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.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07037888

Study Details | NCT07037888 | Efficacy of Ketorolac for ...

The goal of this clinical trial is to learn whether the medication ketorolac can help manage pain after hip arthroscopy as well or better ...

3.

bmcanesthesiol.biomedcentral.com

bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-025-03335-0

Comparing the efficacy of combining ketorolac and ...

RCT, which compare the efficacy of ketorolac and Ibuprofen, the results of our study are similar to Steiness et al. study. Both studies ...

4.

tandfonline.com

tandfonline.com/doi/full/10.1080/17581869.2025.2560293?src=exp-la

Efficacy and adverse effects of lower doses of ketorolac

In acute, postoperative, and cancer pain, there was no difference in the analgesic effect of lower doses of ketorolac in comparison to routine doses. In ...

5.

annemergmed.com

annemergmed.com/article/S0196-0644(23)00298-6/abstract

Comparative Effectiveness of Ketorolac Dosing Strategies ...

In adult ED patients with acute pain, parenteral ketorolac given at doses of 10 mg to 20 mg is probably as effective in relieving pain as doses of 30 mg or ...

6.

pmc.ncbi.nlm.nih.gov

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

Evidence‐based safety profile of oral ketorolac in adults

Reports of the adverse events of ketorolac include upper gastrointestinal complications, 10 renal and cardiovascular function, and bleeding.

7.

systematicreviewsjournal.biomedcentral.com

systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-024-02685-z

The efficacy and safety of ketorolac for postoperative pain ...

Overall, our findings suggest that Ketorolac is most effective in providing clinically meaningful pain relief within the first 6 h after lumbar ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0735675719303869

Safety of parenteral ketorolac use for analgesia in geriatric ...

In summary, this study found no associated increase in the incidence of adverse cardiovascular, gastrointestinal, and renal outcomes with the use of single ...

9.

ncbi.nlm.nih.gov

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

Ketorolac - StatPearls - NCBI Bookshelf

Ketorolac, a nonsteroidal anti-inflammatory drug, is an option for the management of acute moderate-to-severe pain. Ketorolac is available in various forms, ...