Treatment of Gastroesophageal Reflux Disease in Infants- a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 96
- 试验地点
- 3
- 主要终点
- Change from baseline in reflux episodes in the fourth week of active treatment, compared to placebo
研究概览
简要总结
Gastroesophageal reflux disease in infants is not fully understood. Infants are prescribed medical treatments that may not be effective or that contribute to adverse side effects and lead to concerns and expenses for the parents and healthcare system. Current guidelines recommend cow-milk-protein free diet as a first-line treatment, but these recommendations are based on weak evidence. This study investigate the efficacy of a cow-milk-protein free diet compared to treatment with a proton pump inhibitor (omeprazole)
详细描述
An increasing number of infants less than one year of age have been referred to the pediatric departments with gastroesophageal reflux in the past decade. Gastroesophageal reflux is a common condition in infants defined as the passage of gastric contents into the esophagus with regurgitation or vomiting. Around 50% of infants younger than four months regurgitate or vomit regularly. In most cases, it is a harmless, self-limiting condition; in 90% of cases, the symptoms diminish before 12 months. However, if reflux leads to troublesome symptoms or complications, it is defined as gastroesophageal reflux disease. Troublesome symptoms may include failure to thrive, back arching, food refusal, regurgitation, and irritability. The prevalence of gastroesophageal reflux disease varies between studies. Infants can be treated medically, and proton pump Inhibitors have been recommended as the first choice. However, within the last few years, there has been concern among pediatricians that too many infants are unnecessarily treated with this medication. There are only a few randomized studies on proton pump inhibitor treatment in children under one year, and most studies do not show a significant effect on symptoms. Side effects of treatment with proton pump inhibitors include symptoms related to the gastrointestinal tract or airways, increased susceptibility to infections, and increased risk of developing allergy later in life. Within the past years, there has been attention to the overlapping of symptoms between gastroesophageal reflux disease and allergy to cow milk protein. Cow-milk-protein allergy is the most common food allergy in early childhood, with an estimated prevalence of 2-3%, and presents with various symptoms predominantly from the skin and gastrointestinal tract. Consequently, cow-milk-protein allergy can be challenging to differentiate from gastroesophageal reflux disease. Cow-milk-protein-allergy is an immune reaction and can be either immunoglobulin E-mediated, presenting with immediate reaction including anaphylaxis, or non-immunoglobulin E-mediated, presenting with delayed symptoms. In addition, it is possible that cow's milk can aggravate gastroesophageal reflux disease with a non-immunologic mechanism. As there is no biomarker to differentiate non-immunoglobulin E-mediated cow-milk allergy from gastroesophageal reflux disease, the diagnosis of non-immunoglobulin E-mediated cow-milk allergy can only be verified by an oral food challenge test preceded by a cow-milk-protein-elimination period. Therefore, in the updated international guidelines, all children with gastroesophageal reflux disease should start with a 2-4-week cow-milk-protein-elimination diet before a proton pump inhibitor is prescribed. However, evidence is scarce on the effect of a cow-milk-protein-free diet in infants diagnosed with gastroesophageal reflux disease.
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)
盲法说明
The study is partially blinded. There is blinding in relation to the placebo arm and the proton pump inhibitor arm.
入排标准
- 年龄范围
- 1 Month 至 1 Year（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants diagnosed with gastroesophageal reflux disease (GERD)
- •Age < 1 year at the time of referral
- •Age >1 month at start of treatment
- •At least 3 reflux episodes/daily in average
- •At least one of following troublesome symptoms are present: Crying of unknown reason, discomfort/irritability, problems gaining weight/ weightloss, rejects the breast or bottle, apnea, back-arching.
排除标准
- •Children with diagnosed or suspected syndrome /genetic disorder
- •Congenital malformations (minor deformities are excepted)
- •Abdominal surgery
- •Metabolic disease
- •Treatment with proton pump inhibitor within the last week
- •Allergy for proton pump inhibitors
- •Allergy for cow milk protein
- •Infants on Cow's milk free diet
研究组 & 干预措施
Proton pump inhibitor
Omeprazole 1 mg/ kg and continuing nutrition containing cow's milk protein
干预措施: Protein pump inhibitor. (Drug)
Mother or infant diet
Mother on cow milk-protein-free diet if breastfeeding and infant on a hypoallergenic formula if bottle-fed.
干预措施: Mother or infant diet (Behavioral)
Placebo
Placebo medicine (appearing substantially like Omeprazole) 1mg/kg and continuing nutrition containing cow's milk protein
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in reflux episodes in the fourth week of active treatment, compared to placebo
时间窗: Baseline and daily in 4 weeks.
Parent-reported reduction in the weekly number of reflux-episodes in the fourth week of active treatment with either PPI or diet, compared to placebo. The outcome is registered daily in an App.
次要结局
- Change from baseline in reflux episodes in the fourth week in the PPI group, compared to the diet group.(Baseline and 4 weeks)
- Change from baseline in weight(Baseline and 4 weeks)
- Change from baseline in the number of reflux episodes with visible blood(1,2,3,4 weeks)
- Change from baseline in the number of episodes with discomfort(1,2,3,4 weeks)
- Change from baseline in the numbers of episodes with crying(1,2,3,4 weeks)
- Change from baseline in the number of episodes of refusing breast/ bottle(1,2,3,4 weeks)
- Change from baseline in the number of episodes with short breathing pauses(1,2,3,4 weeks)
- Change from baseline in the number of episodes with paleness/blue color in face or lips(1,2,3,4 weeks)
- Change from baseline in the number of episodes with troublesome breathing/cough(1,2,3,4 weeks)
- Immunoglobulin E level(4 weeks after treatment is started)