Lower-dose IV ketorolac for pain control in adults in the ICU

Ketorolac at Lower Doses for Analgesic Pain Control in ICU: A Randomized, Blinded, Parallel-Group, Placebo-Controlled Trial to Ascertain the Effect of Ketorolac on Pain Scores and Opiate Use for Critically Ill Patients

This pilot tests whether adding low-dose intravenous ketorolac to usual care can safely reduce opioid use for adults with pain in the ICU.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Alberta (Academic / other)
• Locations: 1 site (Edmonton, Alberta)
• Trial ID: NCT06819956 on ClinicalTrials.gov

What this trial studies

This single-centre, randomized, placebo-controlled pilot compares intravenous low-dose ketorolac plus usual care versus placebo plus usual care in critically ill adults with pain. The primary goal is to determine feasibility for a larger trial by measuring recruitment, consent, and randomization rates. The protocol also tracks safety endpoints (acute kidney injury and gastrointestinal bleeding) and efficacy signals such as opioid consumption and pain scores. Key exclusions include significant pre-existing kidney disease, new high-grade AKI, recent GI bleeding, hyperkalemia, and ongoing ACEi/ARB use in the ICU.

Who should consider this trial

Good fit: Adult ICU patients with pain (CPOT > 1 or self-reported VAS/NRS > 1) who do not have advanced kidney disease, active high-grade AKI, recent gastrointestinal bleeding, hyperkalemia, or ongoing ACEi/ARB therapy are ideal candidates.

Not a fit: Patients with pre-existing CKD stage >3, current KDIGO stage >2 AKI, elevated serum creatinine or potassium, recent GI bleeding, or who are receiving ACEi/ARB in the ICU are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, this approach could reduce opioid requirements in ICU patients and lower the risk of post-discharge opioid dependence while maintaining acceptable safety.

How similar studies have performed: NSAIDs have shown opioid-sparing effects in surgical and outpatient settings, but their use at lower doses in critically ill ICU patients is relatively novel and not well established.

Eligibility criteria

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)

Where this trial is running

Edmonton, Alberta

• University of Alberta Hospital — Edmonton, Alberta, Canada (Recruiting)

Study contacts

• Principal investigator: Vincent I Lau, MD MSc — University of Alberta
• Study coordinator: Vincent I Lau, MD MSc

Conditions Pain Management; analgesia; ketorolac; NSAID; ICU