30 Participants Needed

Ketorolac for Pain Management

(KETOROLAC-ICU Trial)

VI
Overseen ByVincent I Lau, MD MSc
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: University of Alberta
Must be taking: Stress ulcer prophylaxis
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

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.

What data supports the effectiveness of the drug Ketorolac for pain management?

Research shows that Ketorolac is effective in managing moderate to severe pain after minor or intermediate surgeries, helping patients recover faster with fewer side effects. It also works well when combined with opioids, reducing the need for higher doses of opioids, which can be beneficial in managing pain after major surgeries.12345

Is ketorolac generally safe for pain management in humans?

Ketorolac is generally safe for pain management, but it can cause side effects like stomach bleeding, kidney problems, and allergic reactions, especially in high doses or long-term use. It's important to follow dosage guidelines and avoid use in people with certain conditions like asthma or a history of stomach issues.678910

How is the drug ketorolac unique for pain management?

Ketorolac is unique because it provides strong pain relief similar to opioids but without affecting the central nervous system, making it a safer option with fewer regulations. It works by blocking the production of prostaglandins, which are chemicals in the body that cause pain and inflammation.1112131415

What is the purpose of this trial?

Opiates are commonly used to control pain in critically ill patients in the ICU. However, increased rates of opiate use in hospital may lead to increased prescription-based opiate dependence after leaving the ICU. This may contribute to the ongoing opiate epidemic across the world. Other medications that can reduce pain, like non-steroidal anti-inflammatory drugs (NSAIDs), are being studied in critically ill patients. These drugs block the enzyme, cyclooxygenases (COX), which causes inflammation in the body. Blocking these enzymes can decrease pain, fever, and inflammation. Traditionally, NSAIDs are not commonly used in critically ill patients due to the perceived risk of gastrointestinal (GI) bleeding and acute kidney injury (AKI). However, many critically ill patients are already receiving medications and treatments to prevent GI bleeding and AKI and are closely monitored so these medications may be useful in reducing pain for these patients.The purpose of this study is to see whether NSAIDs can be used safely in critically ill patients to reduce the dose of opiates required for pain control. This is a pilot study or a feasibility study, which is not expected to answer the question definitively. Its main purpose is to determine if NSAIDs could reduce the use of opiates in critically ill patients while in the ICU. The data collected in this study may be used in a larger study in the future.

Research Team

VI

Vincent I Lau, MD MSc

Principal Investigator

University of Alberta

Eligibility Criteria

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
See 25 more

Timeline

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

Treatment Details

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.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: KetorolacExperimental Treatment1 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: PlaceboPlacebo Group1 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).

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials
957
Recruited
437,000+

Findings from Research

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.
Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials.De Oliveira, GS., Agarwal, D., Benzon, HT.[2022]
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.
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]
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.
Minimising the adverse effects of ketorolac.Reinhart, DI.[2018]

References

Analgesic efficacy of ketorolac. [2013]
Comparison of morphine and ketorolac for intravenous patient-controlled analgesia in postoperative cancer patients. [2019]
[Comparison of sublingual ketorolac vs. IV metamizole in the management of pain after same-day surgery]. [2018]
Comparison of efficacy of oral rofecoxib and ketorolac in controlling early postoperative outpatient orthopedic surgical pain. [2014]
Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. [2022]
Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery. [2022]
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. [2018]
Minimising the adverse effects of ketorolac. [2018]
Ketorolac-precipitated asthma. [2019]
10.United Statespubmed.ncbi.nlm.nih.gov
Clinical implications of ketorolac for postoperative analgesia. [2019]
Optimization of structures, biochemical properties of ketorolac and its degradation products based on computational studies. [2023]
Rapid pain relief using transdermal film forming polymeric solution of ketorolac. [2013]
13.United Statespubmed.ncbi.nlm.nih.gov
Prospective randomized trial of ketorolac after congenital heart surgery. [2019]
[Treatment of moderate and severe pain. Ketorolac--a new analgesic]. [2013]
15.United Statespubmed.ncbi.nlm.nih.gov
Safety of ketorolac in surgical neonates and infants 0 to 3 months old. [2013]
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