此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

较低剂量的Ketorolac在ICU中进行镇痛疼痛控制：一项初步可行性研究 (KETOROLAC-ICU)

2026年9月24日 更新者：University of Alberta

较低剂量的Ketorolac在ICU中进行镇痛性疼痛控制：一项随机，盲，平行组，安慰剂对照试验，以确定酮洛拉克对疼痛评分的影响和对重症患者的阿片类药物的影响

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.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

Purpose: The purpose of this study is to determine the feasibility of conducting a future, adequately powered large-scale randomized trial, while evaluating the safety and efficacy of an intravenous NSAID (e.g., ketorolac) plus usual care as compared to placebo plus usual care in critically ill patients.

Hypothesis: The investigators hypothesize that this single-centre pilot study will demonstrate that NSAIDs administration is feasible and safe in ICU patients and may potentially reduce opiate use in ICU patients with pain.

Justification: Pain control in ICU is difficult to achieve given that opiates are the mainstay of analgesia in critically ill patients, but this is not without unintended side effects, especially unintended consequences of possible future drug dependence or addictions. Given that opiates and other adjunctive pain medications (e.g., acetaminophen) are being utilized at high proportional rates, and that NSAIDs are used at relatively low rates (due to the theoretical risk of increased AKI and GI bleeds), there is potential for practice change for increased NSAID use at lower doses to reduce pain and opiate use, while not increasing risks.

Objectives: The primary objective of this pilot trial is to assess the feasibility of a larger clinical trial utilizing NSAIDs in the ICU for patients with pain. The primary outcomes of the pilot feasibility trial are: recruitment and consent rates, proportion of eligible participants who are randomized vs. not randomized, retention and protocol adherence rates.

The secondary objectives are to assess safety of the proposed trial (e.g. gastrointestinal bleeding, acute kidney injury, death) and efficacy outcomes (e.g. participant pain scores, opiate and other analgesia usage).

Research Methods/Procedures: The investigators have designed KETOROLAC-ICU as a pilot randomized controlled trial (prospective, single centre, parallel-group, concealed, blinded) examining the use of low-dose ketorolac for critically ill patients.

研究类型

介入性

注册 (估计的)

30

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 加拿大
    • Alberta
      • Edmonton、Alberta、加拿大、T6G 2B7
        • 招聘中
        • University of Alberta Hospital
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

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)

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：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).
药品：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.
安慰剂比较：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).
药品：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.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Feasibility - Recruitment and Retention
大体时间：Days 1-7, 90

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
大体时间：Days 1-7, 90

Rates of protocol adherence and reasons for protocol non-adherence.
Days 1-7, 90

次要结果测量

结果测量
措施说明
大体时间
Opioid Use
大体时间：Baseline; Days 1-7, 14, 21, 28, 90

The administration of opioid medications (converted into oral morphine equivalents)
Baseline; Days 1-7, 14, 21, 28, 90
Pain Scores - Critical Care Pain Observation Tool (CPOT)
大体时间：Baseline; Days 1-7, 14, 21, 28

The critical care pain observation tool (CPOT) is used by healthcare workers to measure four indicators of pain: facial expression, body movements, muscle tension, and compliance with the ventilator (or vocalization for extubated participants). Each of the four indicators are ranked from 0 to 2, with higher numbers describing more pain behaviors.
Baseline; Days 1-7, 14, 21, 28
Pain Scores - Visual Analog Scale (VAS)
大体时间：Baseline; Days 1-7, 14, 21, 28

The visual analog scale (VAS) is a self-reported measure of a participant's level of pain. This tool consists of a single, 10cm long line, with one end titled "No pain" and the other end titled "Pain as bad as it could possibly be." The participant then draws a mark on the line that corresponds to their level of pain. This mark is later quantified in distance from the "no pain" side of the line.
Baseline; Days 1-7, 14, 21, 28
Pain Scores - Numerical Pain Rating Scale (NRS)
大体时间：Baseline; Days 1-7, 14, 21, 28

The numerical pain rating scale (NRS) is a self-reported measure of a participant's level of pain. Participants are asked to rank their pain on a scale of 0 to 10, with 0 representing no pain, and 10 representing the worst possible pain.
Baseline; Days 1-7, 14, 21, 28
Safety - Acute Kidney Injury
大体时间：Days 1-7, 28

KDIGO Stage ≥ 2 (increased serum creatinine > 2-3 times above baseline AND/OR <0.5mL/kg/hour urine output for >12 hours) AND/OR need for renal replacement therapy
Days 1-7, 28
Safety - Gastrointestinal (GI) Bleeding
大体时间：Days 1-7, 28

Clinically significant GI bleeding (visual and physiological evidence of overt GI bleeding)
Days 1-7, 28
Safety - Other
大体时间：Days 1-28

Occurrence of any adverse and/or serious adverse events
Days 1-28
All-Cause Mortality
大体时间：Days 28, 90

All-cause mortality in ICU, in hospital, or post-discharge.
Days 28, 90
Health-Related Quality of Life (EQ-5D-5L)
大体时间：Day 90

EuroQol's Health-Related Quality of Life questionnaire (EQ-5D-5L) is a self-reported measure of a participant's current health status and quality of life. This questionnaire consists of 5 questions, each representing a different dimension of health-related quality of life: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each question has 5 possible responses, ranging from "no problem" (score of 1) to "unable/extreme problems" (score of 5).
Day 90
Clinical Frailty Scale (CFS)
大体时间：Baseline; Day 90

The Clinical Frailty Scale (CFS) is a tool to describe a participant's frailty and level of functioning. This scale ranges from "Very Fit" (score of 1) to "Terminally Ill" (score of 9).
Baseline; Day 90
Cognitive Measures
大体时间：Days 1-28

Delirium incidence (ICDSC scores ≥ 4), duration of decreased level of consciousness (LOC) due to moderate-severe sedation (RASS scores ≤ -3), duration of decreased LOC requiring intubation or ongoing mechanical ventilation (GCS < 8)
Days 1-28
Organ Support
大体时间：Days 1-7, 14, 21, 28, 90

Use and duration of invasive mechanical ventilation (including rates of reintubation), non-invasive ventilation, renal replacement therapy, and vasopressors
Days 1-7, 14, 21, 28, 90
Length of Admission
大体时间：Day 90

ICU length of stay, hospital length of stay, readmission episodes
Day 90
Procedures
大体时间：Days 1-7, 28

Need for endoscopy (EGD or colonoscopy), angiography, and/or exploratory laparotomy
Days 1-7, 28
Other Analgesia
大体时间：Days 1-7, 14, 21, 28, 90

Administration of non-opioid analgesic medications
Days 1-7, 14, 21, 28, 90

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

University of Alberta

调查人员

  • 首席研究员：Vincent I Lau, MD MSc、University of Alberta

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2025年6月23日

初级完成 (估计的)

2026年12月1日

研究完成 (估计的)

2027年12月1日

研究注册日期

首次提交

2025年1月30日

首先提交符合 QC 标准的

2025年2月5日

首次发布 (实际的)

2025年2月11日

研究记录更新

最后更新发布 (实际的)

2026年9月28日

上次提交的符合 QC 标准的更新

2026年9月24日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • Pro00126948

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅