Ketorolac at Lower Doses for Analgesic Pain Control in ICU: A Pilot Feasibility Study

NCT06819956 | Recruiting Phase 3 DMC

• 1 other identifier: Pro00126948
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Keywords

analgesia; ketorolac; NSAID; ICU

Outcome Measures

Primary Outcomes (2)

• Feasibility - Recruitment and Retention

  Recruitment rate at pilot site (participants/month), consent rates of eligible participants, proportion of eligible participants not randomized, and participant retention rates.

  Days 1-7, 90

• Feasibility - Protocol Adherence

  Rates of protocol adherence and reasons for protocol non-adherence.

  Days 1-7, 90

Secondary Outcomes (15)

• Opioid Use

  Baseline; Days 1-7, 14, 21, 28, 90

• Pain Scores - Critical Care Pain Observation Tool (CPOT)

  Baseline; Days 1-7, 14, 21, 28

• Pain Scores - Visual Analog Scale (VAS)

  Baseline; Days 1-7, 14, 21, 28

• Pain Scores - Numerical Pain Rating Scale (NRS)

  Baseline; Days 1-7, 14, 21, 28

• Safety - Acute Kidney Injury

  Days 1-7, 28

Study Arms (2)

Ketorolac

EXPERIMENTAL

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).

Drug: Ketorolac

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

Ketorolac DRUG

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.

Ketorolac

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[NRS\])

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

RECRUITING

MeSH Terms

Conditions

Agnosia

Interventions

Ketorolac

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Vincent I Lau, MD MSc

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent I Lau, MD MSc

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2025
• First Posted: February 11, 2025
• Study Start: June 23, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

CA (1)