Nebulized N-Acetyl Cysteine for Bronchiolitis in Inpatient Hospital Use: A Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 入组人数
- 106
- 试验地点
- 1
- 主要终点
- Time on Non-Invasive Ventilation
研究概览
简要总结
Bronchiolitis is the major cause of hospital admission in infants < 6 months of age and usually viruses like Respiratory syncytial virus (RSV), human metapneumo virus, Adeno virus, para-influenza virus, Rhino virus and influenza virus are the main culprit. In the US, acute bronchiolitis in infancy is responsible for approximately 150,000 hospitalizations yearly at an estimated cost of $500 million. Globally in 2005 it was estimated that at least 33.8 million were affected with RSV and in the same year, RSV associated severe acute lower respiratory infection (ALRI) were responsible for ~3.4 million hospitalizations and 66,000-199,000 deaths worldwide, with 99% of these deaths in developing countries.
In acute bronchiolitis there is cellular swelling and excessive mucus production. There is also proliferation of goblet cells, which leads to increased mucus production. The excess mucus produced is poorly cleared by non-ciliated (regenerating) epithelial cells leading to areas of narrowing and blocking of the bronchioles, causing the airway obstruction, hyperinflation, increased airway resistance, atelectasis and increased ventilation-perfusion mismatch that characterize acute bronchiolitis.
Currently there is no medicine that has proven effective in treating acute bronchiolitis and per American Academy of Pediatrics guidelines the management of acute bronchiolitis remains supportive care for the acute respiratory failure associated with acute bronchiolitis.
N-Acetyl Cysteine (NAC) is an antioxidant, anti-mucus compound that increases intracellular glutathione at the cellular level. It cleaves disulfide bonds by converting them to two sulfhydryl groups. This action results in the breakup of mucoproteins in lung mucus, reducing their chain lengths and thinning the mucus. Nebulized NAC is not studied well in acute bronchiolitis and is uncommonly used for the same. NAC has been studied in the treatment of various disease states, including those pulmonary in nature such as cystic fibrosis, chronic bronchitis, non-cystic fibrosis bronchiectasis and found to be beneficial.
With this background knowledge, the purpose of this study is to evaluate the effectiveness of nebulized mucolytic therapy in treatment of children with viral bronchiolitis.
详细描述
A randomized clinical trial with blinding of person assigned for assessing and scoring the patients. The participants will include children less than 2 yrs. age admitted to the Pediatric Intensive Care Unit (PICU) with a diagnosis of acute bronchiolitis who will be randomized into either the NAC group or the non-NAC (Control) group.
Patients with acute bronchiolitis who require to be started on high flow nasal cannula support or any other noninvasive ventilator/BIPAP support are transferred/directly admitted to PICU. There is no time limit between when patients are admitted and when patients must sign consent or be randomized.
After a patient with acute bronchiolitis is identified, a member of the study team will perform a chart review to assess eligibility as described by the inclusion/exclusion criteria. If eligible, parent(s)/guardian(s) will be approached and Informed Consent will be obtained. Using randomization software(www.randomizer.org) the enrolled patients will be randomly assigned to either the NAC group or the non-NAC (Control) group.
The NAC will be ordered by the on call pharmacist and it will be administered by the on call Respiratory therapists. Between the two groups only the NAC group will get nebulized 2 ml of 10% NAC solution every 12 hours during their stay in PICU.
The PICU uses HHFNC (humidified high flow nasal canula), Heliox and non-invasive ventilation such as RAM canula, Neurally adjusted ventilatory assist (NAVA) and BIPAP. The PICU also typically uses Dexmedetomidine infusion once the patient is on non invasive ventilation (NIV) as a light sedation medication to avoid agitation and better ventilation patient synchrony.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Week 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Full term new born neonates up to patients < 2yrs
- •Respiratory score ≥2
- •Otherwise healthy with new respiratory illness
排除标准
- •Prematurity <34 weeks for patients <6 months age.
- •h/o congenital heart disease requiring baseline medication
- •Patient received diagnosis of Asthma or reactive airway disease in past.
- •Anatomic airway defect.
- •Immunodeficiency
- •Chronic lung disease
- •Patients who have had previous bronchiolitis < 4 weeks ago
- •Patients intubated for acute bronchiolitis during the current admission.
- •h/o Larynogomlacia, bronchomalacia or tracheomalacia.
研究组 & 干预措施
Treatment Group
Subjects will receive N-Acetyl Cysteine (NAC) nebulized 2 mL of 10% NAC solution every 12 hours during their stay in the Pediatric Intensive Care Unit.
干预措施: N-Acetyl Cysteine (Drug)
结局指标
主要结局
Time on Non-Invasive Ventilation
时间窗: From time of PICU admission to time of PICU discharge, assessed up to 4 weeks
Length of time on NIV
Duration of PICU/Hospital Admission
时间窗: From time of hospital admission to time of hospital discharge, assessed up to 4 weeks
Length of time patient remains hospitalized
Respiratory Score
时间窗: 1. Twice daily by physician 2. 15-30 min pre-treatment by nurse 3. 15-30 and 90 min post-treatment by nurse
4 item scoring system completed by clinician used to assess respiratory symptoms. Each item is scored 0-3, with the value increasing as severity of symptoms increases.
次要结局
未报告次要终点
研究者
Rahul Pandey
Assistant Professor, Pediatric Critical Care Medicine
Carilion Clinic