Pragmatic RCT of High-dose Oral Montelukast for Moderate and Severe Pediatric Acute Asthma Exacerbations
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- Change of percent-predicted airway resistance at 5Hz (%R5) by impulse oscillometry
研究概览
简要总结
Objective: To determine the extent to which high-dose (30mg) oral montelukast, added to standard treatment in children with moderate and severe acute exacerbations improves outcomes.
Central Hypothesis: High-dose oral montelukast, added to standard treatment in children aged 5 to 17 years with moderate and severe acute asthma exacerbations, rapidly improves lung function, clinical severity, hospitalization rate and 72-hour symptom burden.
Secondary Hypotheses:
- There are greater effects of high-dose oral montelukast on lung function and on the secondary outcomes in the presence of respiratory viral detection or leukotriene-mediated inflammation; and
- There is an interaction between viral detection and urinary leukotriene 4 level with treatment-response.
Design: A two-arm, parallel randomized controlled trial of high-dose oral montelukast versus identical placebo, as add-on to standard treatment, in children aged 5 to 17 years with moderate and severe acute asthma exacerbations.
Intervention: High-dose oral montelukast added to standard treatment in comparison with standard treatment as the 2nd treatment-allocation arm.
Primary and Important Secondary Endpoints: For the Primary Aim, the primary outcome measure to be compared between arms will be change of %-predicted airway resistance by impulse oscillometry (IOS) at 5Hz (%R5) at 2 hours after treatment initiation. Secondary outcomes will include improvement of %-predicted FEV1 (%FEV1), clinical severity measured using the validated Acute Asthma Intensity Research Score (AAIRS), hospitalization rate, and 72 hour symptom burden using the Pediatric Asthma Caregiver Diary (PACD). For the Secondary Aim, the investigators will determine (1) The effects of high-dose oral montelukast on lung function and on our secondary outcomes in the presence of nasal viruses and of greater leukotriene-mediated inflammation; and (2) The degree of interaction between viral detection and urinary leukotriene E4 (LTE4) level with treatment-response.
Laboratory evaluations: The primary outcome (change of %R5) and select secondary outcomes (%FEV1, AAIRS, LTE4) will be measured before and again at 2 hours after treatment initiation. The other secondary outcomes will be measured at the time of hospitalization decision-making by the clinical team (hospitalization rate) or at 72-hours after treatment initiation (PACD).
详细描述
Study overview: The approach to testing the central hypothesis will be to conduct a two-arm, parallel randomized controlled trial of high-dose (30mg) montelukast versus identical placebo, as add-on to standard treatment of SCS and inhaled SABA, in children aged 5 to 17 years with moderate and severe acute asthma exacerbations. Although this aim will enable us to test each hypothesis, the ability to test each hypothesis is independent of the others.
Randomization: The investigators will use randomly-permuted blocks of 4 to 8 to minimize seasonal bias of exacerbation precipitants that may have independent associations with treatment-response.
Masking of treatment-allocation and outcome-ascertainment: Investigator or clinical team knowledge of treatment allocation may influence assessment of outcomes. Allocation concealment will minimize this bias. The investigators will adhere to established procedures to maintain masking of participants, CTAs, and data analysts.
Aim 1: Testing the primary hypothesis The investigators will measure lung function before and after 2-hours of treatment using airway resistance by impulse oscillometry at 5Hz (%R5).
Expected outcomes of the primary aim: The investigators expect that high-dose montelukast will result in a minimum 15% greater improvement in %R5 and a 10% improvement of %FEV1 between pre-treatment and 2-hours after dosing in comparison with standard treatment. The investigators base this expectation on (1) The known contribution of leukotrienes to airway inflammation during acute asthma exacerbations;8-11 (2) Knowledge that corticosteroids do not inhibit leukotriene synthesis in vivo;7 (3) High-quality trials of IV montelukast in patients with moderate and severe acute asthma exacerbations by Camargo and colleagues that demonstrated rapid and sustained improvement of lung function and decreased need for SCS;25,26 and (4) The pharmacokinetics of IV and oral montelukast indicating that serum levels after high-dose oral montelukast are comparable to the IV doses used in the Camargo trials.29,69-72 The investigators expect that high-dose montelukast will result in meaningful improvement of clinical severity, hospitalization rate, and 72-hour symptom burden.
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
Study drug (montelukast granules) and identical control will be prepared by the Vanderbilt Investigational Drug service. Participants will be randomized by computerized program by study biostatistician.
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
High-dose Montelukast Oral Granules
30 mg (high-dose) oral montelukast granules mixed in apple sauce will be administered orally immediately after informed consent and assent are obtained.
干预措施: Montelukast Oral Granules (Drug)
Placebo
Identical placebo mixed in apple sauce will be administered orally immediately after informed consent and assent are obtained.
干预措施: Montelukast Oral Granules (Drug)
结局指标
主要结局
Change of percent-predicted airway resistance at 5Hz (%R5) by impulse oscillometry
时间窗: Before and 2-hours after treatment with montelukast or placebo
Change of percent-predicted airway resistance at 5Hz (%R5) by impulse oscillometrypost montelukast or control administration
次要结局
- Leukotriene E4 (LTE4)(Before treatment with montelukast or placebo)
- Change of percent-predicted forced expiratory volume in 1-second (FEV1)(Before and 2-hours after treatment with montelukast or placebo)
- 72-hours symptom burden measured using the pediatric asthma caregiver diary (PACD)(Before and at 72-hours after treatment with montelukast or placebo)
- Hospitalization rate(8-hours after treatment with montelukast or placebo)
- Change of the Acute Asthma Intensity Research Score (AAIRS)(Before and 2-hours after treatment with montelukast or placebo)
研究者
Donald Hayes Arnold
Professor of Pediatrics and Emergency Medicine
Vanderbilt University Medical Center