Recruiting
Phase 3

NSAIDs

Sponsor:

University of Alberta

Code:

NCT06819956

Conditions

Pain Management

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Ketorolac

Placebo

Study Details

Brief summary:

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.

Conditions

Pain Management

Study ID

NCT06819956

Start date

Jun 23, 2025

Status verified date

Sep, 2025

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age > 18 years
  • Admission to intensive care unit (ICU)
  • Participants with pain (Critical Care Pain Observation Tool \[CPOT\] > 1 and/or self-report pains score >1 on visual analogue scale \[VAS\] or numerical rating scale \[NRS\])

Exclusion Criteria:

  • Serum Cr > 100 mmol/L for females, and >130 mmol/L for males
  • Ongoing ACEi (angiotensin converting enzyme inhibitor)/ARB (angiotensin receptor blocker) use in ICU
  • Known hyperkalemia > 5.5
  • Pre-existing chronic kidney disease (CKD Stage > 3), defined by a serum Cr > 100 mmol/L for females, and >130 mmol/L for males (at the time of screening, based on pre-hospital stable outpatient baseline values)
  • New acute kidney injury KDIGO Stage > 2 (increased more than > 2-to-3 times in serum creatinine above baseline AND/OR <0.5mL/kg/hour urine output for >12 hours)
  • Pre-existing gastrointestinal bleeding (within 12 weeks of hospital admission, requiring hospitalization or medical evaluation), new peptic ulcer disease, esophagitis, esophageal varices within the last 3 months
  • Active gastric / duodenal / peptic ulcer, active GI bleeding
  • Prior contraindications/allergies to NSAIDS or stress ulcer prophylaxis, specifically if a participant has had an anaphylactic reaction (asthma or urticaria) or non-anaphylactic asthma reaction to NSAIDs or any stress ulcer prophylaxis, e.g. proton pump inhibitor, histamine-2-blockers, etc. (e.g. proton pump inhibitor, histamine-2-blockers, etc.)
  • Complete or partial syndrome of ASA-intolerance (e.g. rhinosinusitis, urticaria/angioedema, nasal polyps, asthma)
  • Participants who are not receiving stress ulcer prophylaxis (e.g. proton pump inhibitor, histamine-2-blockers, etc.) while in ICU
  • Any active bleeding (requiring any blood products or adjunctive coagulation agents, any output of blood >100 mL/hr, e.g. chest tube drainage, abdominal cavity drain, etc.)
  • Currently receiving NSAID(s) for another indication
  • Inflammatory bowel disease (e.g. participants with prior diagnosis of Crohn's disease or ulcerative colitis)
  • Receiving probenecid, oxpentifylline or pentoxifylline
  • Active ischemic heart disease (acute myocardial infarction, acute coronary syndrome during current hospital admission)
  • Moderate-severe uncontrolled heart failure (New York Heart Association: Class II-IV)
  • Moderate to severe liver impairment or active liver disease (Operational definition: participants with prior history of Child-Pugh class B (moderate) or C (severe) liver cirrhosis, OR Model for End-Stage Liver Disease-Sodium (MELD-Na) score >25, OR active acute liver failure: severe acute liver injury with encephalopathy and impaired synthetic function International Normalized Ratio (INR) >1.5 with or without pre-existing liver disease)
  • Active cerebrovascular bleeding or stroke (cerebrovascular accident, transient ischemic attacks and/or amaurosis fugax, e.g. participants with active stroke symptoms within current hospital admission)
  • Cerebrovascular bleeding or other bleeding disorders
  • Coagulation disorders, post-operative patients with high haemorrhagic risk or incomplete haemostasis in patients with suspected or confirmed cerebrovascular bleeding
  • Neuraxial (epidural or intrathecal) administration of ketorolac tromethamine injection due to its alcohol content
  • Rhabdomyolysis (creatinine kinase >5000 U/L)
  • Recent transplant (during same hospital admission, e.g., heart, lung, kidney, liver, etc.)
  • Known allergy to ketorolac or other NSAIDs
  • Participants expected to stay in ICU < 48 hours
  • In the opinion of the attending physician, expected death or withdrawal of life-sustaining treatments within 48 hours
  • Participant is known to be pregnant and/or breastfeeding
  • Most responsible physician, participant, or substitute decision maker declines study participation (and reason)

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Ketorolac

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).

placebo comparator: Placebo

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).

Interventions

Ketorolac

Ketorolac 15 mg IV q6h for a maximum of 3 days total or discharge from ICU (whichever comes first). The ketorolac will be diluted in a 0.9% normal saline 10 mL syringe.

Placebo

Matching placebo IV q6h for a maximum of 3 days total or discharge from ICU (whichever comes first). The matching placebo will be diluted in a 0.9% normal saline 10 mL syringe.

Primary outcome measure

  • Feasibility - Recruitment and Retention [ Time Frame: Days 1-7, 90 ]
  • Feasibility - Protocol Adherence [ Time Frame: Days 1-7, 90 ]

Central Contacts and Locations

Central contacts

Vincent I Lau, MD MSc

780-492-9390vince.lau@ualberta.ca

Locations

University of Alberta Hospital

Recruiting

Edmonton, Alberta, Canada, T6G 2B7

Contacts

Vincent I Lau, MD MSc

780-492-9390vince.lau@ualberta.ca

More Information

Sponsor

University of Alberta

Last update posted

Sep 23, 2025

Last verified

Sep, 2025

Keywords

  • analgesia
  • ketorolac
  • NSAID
  • ICU

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Alberta on 2025-09-23.