Randomized Controlled Trial Evaluating the Additive Value of Intranasal Fentanyl on Ibuprofen in the Pain Management of Children With Moderate to Severe Headaches
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- The primary outcome measure will be the difference of the subjects' self-reported pain scores as assessed by the VAS at the fifteenth minute after administration of the initial drug therapy, which correspond to its peak analgesic effect.
研究概览
简要总结
Background : Headaches are a common presentation for children consulting to the Emergency Department (ED). However, only few studies have evaluated the rapid pain improvement provided by medications in the acute management of headaches in the pediatric population.
Objective : To evaluate pain reduction provided by intranasal fentanyl (INF) compared to placebo in addition to ibuprofen for children presenting to a pediatric ED with moderate to severe headaches.
Methods : A single-center, double-blind, randomized, placebo controlled clinical trial will be conducted in an urban, university-affiliated, tertiary care pediatric hospital ED. All children eight to 18 years old who will present to the ED with headaches as a main chief complaint and with pain of ≥ 36 mm out of 100 on Visual Analog Scale (VAS) will be recruited. Study participants will be randomly allocated to receive INF 1.5 mcg/kg (maximum dose of 100 mcg) or similar volume of a placebo solution via an atomizer. Co-administration of oral ibuprofen 10 mg/kg (maximum dose of 600 mg) will also be provided to the two groups if not received in the previous 4 hours. The primary outcome will be the mean pain rating reduction at 15 minutes. The secondary outcomes will be mean pain reduction at 30 and 60 minutes, patient's and parental satisfaction levels, percent of being pain free, sedation score, immediate and within 72 hours adverse events, additional ED analgesics and other medications, length of ED stay, disposition outcomes, hospital admission rate and ED revisit rate within 72 hours. The primary analysis will use an intention-to-treat approach to compare mean pain score reduction between the two groups using a Student's T-test. The sample size of 60 participants per arm was calculated to have a power of 80% to identify a difference of 10 mm in the VAS.
Expected results : Our study might demonstrate that INF provides additional pain relief for children presenting to an ED with headaches. Providing INF could relieve their symptoms more quickly, potentially improve patient's and family's satisfaction, possibly reduce the length of their ED stay and consequently, have a significant impact on patient quality of care and cost-effectiveness.
详细描述
The primary objective of the present study would be to determine the additive value on analgesic effectiveness of INF in children aged eight to 18 years with acute moderate to severe headaches. We would also aim to gather information on the safety and acceptability of INF for headaches. We believe that providing INF for moderate to severe headaches will decrease pain levels in children aged 8 to 18 years old.
We will perform a prospective, double-blind, randomized placebo-controlled clinical trial.
The study setting will be a single center, urban, university-based, tertiary care pediatric university-affiliated hospital ED with an annual census of 75,000 patient visits. The study should be conducted between 2015-2018.
Study population : Inclusion criteria will consist of children aged eight to 18 years who present to the pediatric ED with a chief complaint of headaches, regardless of the type, with a moderate or severe pain score. Pain was considered at least moderate if superior or equal to 36 mm on the VAS as demonstrated by Hirschfeld et. Al. This level have been chosen because it has been recognized that adequate sensitivity in analgesia trials for acute pain can only be obtained if patients experience at least moderate pain before administration of any treatment.
Intervention: All patients will receive a 1.5 mcg⁄kg dose of fentanyl or an equivalent volume of similar looking placebo. This will be administered intranasally via a mucosal atomiser device (MAD) using 50 mcg/mL solution with a 2 mL syringe. Prior studies have shown that this dose is as effective as IV or IM morphine and provides a bioavailability which is 71% of the IV dose. The minimum dose prescribed will be 20 mcg, to ensure delivery of 15 mcg of fentanyl to a 10 kg child, allowing for the MAD dead space of 0.1 mL (5 mcg of fentanyl). For analgesic dose-volumes equal to and less than 0.5 mL, the entire dose will be administered in one nostril; doses above 0.5 mL will be divided equally and administered to both nostrils. Concentrated medications in a small volume (0.2-0.3 mL per nostril) are ideal, whereas volumes in excess of 1 mL per nostril are not reliably absorbed as a result of mucosal surface saturation and runoff from the nasal cavity. The maximum dose administered will be 100 mcg due to volume constraints. The placebo solution will consist of normal saline that would be delivered via the proposed atomiser. The value administered will be adjusted to the patients weight as for the active study medication. No additional dose of either study medication would be provided. A MAD have been chosen because it is suggested to increase the mucosal coverage and absorption of the medication by atomizing particles and decreasing the amount of medication lost due to swallowing.
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)
入排标准
- 年龄范围
- 8 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria will consist of children aged eight to 18 years who present to the pediatric ED with a chief complaint of headaches, regardless of the type, with a moderate or severe pain score.
- •Pain was considered at least moderate if superior or equal to 36 mm on the VAS as demonstrated by Hirschfeld et. Al. This level have been chosen because it has been recognized that adequate sensitivity in analgesia trials for acute pain can only be obtained if patients experience at least moderate pain before administration of any treatment.
排除标准
- •Allergy or any contra-indication to opioids and-or ibuprofen
- •Previous participation in study to preserve the statistic independence of each participant
- •Caregiver unable to provide consent (language barrier or lack of caregiver presence)
- •Circumstance which, in the opinion of the investigator, would adversely affect their participation in the trial such as a medical or psychiatric condition or a language barrier (neither French or English)
- •Nasopharyngeal anomalies, blockage or traumatized preventing nasal administration
- •Suspicion of life-threatening illness such as acute intracranial haemorrhage, meningitis, encephalopathy, or intracranial cerebral vascular occlusion
- •Signs of intracranial pressure or suspicion of intracerebral process such as mass or tumors (altered mental status, focal neurological deficit, etc.)
- •Any head injury with possible associate intracranial injury in the past 14 daysRecent or acute head injury
- •Current opioid use or opioid antagonist use
- •Intoxication
研究组 & 干预措施
Intranasal Fentanyl
All patients will receive a 1.5 mcg⁄kg dose of fentanyl or an equivalent volume of similar looking placebo. This will be administered intranasally via a mucosal atomiser device (MAD) using 50 mcg/mL solution with a 2 mL syringe.
干预措施: Fentanyl (Drug)
Salinex
All patients will receive a 1.5 mcg⁄kg dose of fentanyl or an equivalent volume of similar looking placebo. This will be administered intranasally via a mucosal atomiser device (MAD) using 50 mcg/mL solution with a 2 mL syringe.
干预措施: Salinex (Other)
结局指标
主要结局
The primary outcome measure will be the difference of the subjects' self-reported pain scores as assessed by the VAS at the fifteenth minute after administration of the initial drug therapy, which correspond to its peak analgesic effect.
时间窗: 15 minutes
次要结局
未报告次要终点
研究者
Serge Gouin
Associate Professor
St. Justine's Hospital