Intravenous Ketorolac Vs. Morphine In Children Presenting With Acute Abdominal Pain And/or Suspected Appendicitis: A Multi-centre Non-Inferiority Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 495
- 试验地点
- 1
- 主要终点
- Pain relief as measured on the verbal numerical rating scale
研究概览
简要总结
Appendicitis is a common condition in children 6-17 years of age, and the top reason for emergency surgery in Canada. Children with appendicitis can have very bad pain in their belly. Children often need pain medications given to them through a needle in their arm called an intravenous (IV). The most common IV pain medication is a type of opioid called morphine. We know that opioids work well to improve pain, but there are risks and side effects when taking them. There are non-opioid medications that doctors can give to patients, like ketorolac. Ketorolac helps decrease inflammation and pain and has fewer side effects when a patient takes it for a short period of time. Our past and present overuse of opioids, driven by an unproven assumption that opioids work best for pain, resulted in an Opioid Crisis and doctors are now looking for alternatives. To do this, we need to prove that there are other options to treat children's pain that are just as good as opioids, with less side effects.
The goal of our study is to discover if school aged children who arrive at the emergency department with belly pain, improve just as much with ketorolac as they do with morphine. To answer this question, we will need a very large number of patients in a study that includes several hospitals across Canada. With a flip of a coin, each participant will either get a single dose of morphine or a single dose of ketorolac. To make sure that our pain assessment is impartial, no one will know which medicine the child received except the pharmacist who prepared the medicine.
详细描述
Background: Appendicitis, the most common surgical diagnosis in Canadian children aged 6-17 years, accounts for ~8000 admissions annually. Despite an ongoing opioid crisis, prescription narcotics remain a mainstay analgesic for children with suspected appendicitis. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), which has a safer adverse event (AE) profile than opioids, is commonly used in emergency departments (EDs) for adults; however, use in children is considered off label due to a lack of randomized trials in this patient population. We propose a multi-centre clinical trial to address this knowledge gap,informed by our team's successful pilot trial.
Specific Aim 1: To determine if administering intravenous (IV) ketorolac is non inferior to IV morphine in reducing mean pain scores in children with suspected appendicitis.
Hypothesis: IV ketorolac will be non-inferior to IV morphine
Specific Aim 2: To determine between group differences in rates of AEs. Hypothesis: IV ketorolac will be associated with less AEs than IV morphine.
Design: A randomized quadruple blind (participant, clinician, outcome assessor, investigator) parallel group double-dummy trial in 4 Canadian pediatric EDs. Eligible patients will be 6-17 years with 5-days of moderate-severe pain (vNRS ≥5 ) being investigated for suspected appendicitis, with intravenous (IV) access, will be randomized to either:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double dummy design
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6 to 17 years
- •Abdominal pain ≤5 days duration
- •Acute abdominal pain that is being investigated (suspected) by the clinical team for appendicitis
- •Patient with IV cannula in situ or ordered
- •Currently experiencing moderate to severe abdominal pain at rest or with movement: self-reported pain score ≥5 using the verbal Numerical Rating Scale
排除标准
- •Previous enrollment in the trial
- •NSAID use within 3 hours and/or opioid use within 1 to 2 hours (1 hour post-IV or intra-nasal fentanyl and 2 hours post IV morphine).
- •Children who need immediate resuscitation, are hemodynamically unstable as deemed by the clinical team or have a Canadian Triage Assessment Score of 1
- •Significant caregiver and/or child cognitive impairment precluding the ability to complete study questions.
- •Chronic pain requiring daily analgesic use: confounding as response to analgesics maybe altered.
- •History of severe undiagnosed gastrointestinal bleeding requiring medical intervention, peptic or duodenal ulcer disease or inflammatory bowel disease, coagulation disorders, prior cerebrovascular bleeding, known arterio-vascular malformations. History of minor gastrointestinal bleeding from conditions such as resolved fissures, polyps or allergic colitis will not exclude patients from participating.
- •History of chronic and active interstitial kidney disease
- •History of chronic and active hepatocellular disease: ketorolac is metabolized by the liver.
- •Known or suspected pregnancy at the time of enrollment or breastfeeding females
- •Known hypersensitivity to NSAIDs or opioids.
- •Absence of a parent/guardian for children who are <16 years of age if they are not a mature minor.
- •Inability to obtain consent due to a language barrier and the absence of language translator in person or by a phone translation service available in the ED.
研究组 & 干预措施
Ketorolac Tromethamine
Ketorolac tromethamine, an NSAID belonging to a group of non-opioid analgesics that inhibit the synthesis of prostaglandins and thromboxanes with strong analgesic and anti-inflammatory properties. It is the only non-opioid parenteral non-sedating analgesic available in Canada for use to treat acute pain in the emergency department.
干预措施: Ketorolac Tromethamine (Drug)
Ketorolac Tromethamine
Ketorolac tromethamine, an NSAID belonging to a group of non-opioid analgesics that inhibit the synthesis of prostaglandins and thromboxanes with strong analgesic and anti-inflammatory properties. It is the only non-opioid parenteral non-sedating analgesic available in Canada for use to treat acute pain in the emergency department.
干预措施: Normal saline (Drug)
Morphine Sulfate
An intravenous opioid that is commonly used as part of usual care for treament of pain in patients with acute abdominal pain and suspected appendicitis.
干预措施: Morphine Sulfate (Drug)
Morphine Sulfate
An intravenous opioid that is commonly used as part of usual care for treament of pain in patients with acute abdominal pain and suspected appendicitis.
干预措施: Normal saline (Drug)
结局指标
主要结局
Pain relief as measured on the verbal numerical rating scale
时间窗: 60 minutes post drug administration
Between group mean differences in pain as measured on an 11-point verbal Numerical Rating Scale (0 is no pain and 10 is worst pain ever)
次要结局
- Pain relief as measured on the verbal numerical rating scale during the ultrasound diagnostic(up to 6 hours post drug administration)
- Proportion who achieve the minimal important difference for pain relief(120 minutes post drug administration)
- Additional analgesia requirment(up to 6 hours post drug administration)
- Adverse events per participant(up to 6 hours post drug administration)
- Pain relief as measured on the verbal numerical rating scale(6 hours post drug administration)
- Change in baseline pain category(6 hours post drug administration)
- Time to effective analgesia(up to 6 hours post drug administration)
- Total opioids administered(up to 8 hours post drug administration)
- Frequency of each specific adverse event(up to 6 hours post drug administration)
- Ramsay sedation score(120 minutes post drug administration)