Use of the bacterial lysate OM-85 for the primary prevention of wheezing lower respiratory illness in preschool children: a randomised, placebo-controlled trial.

We report the results of the ORBEX trial which evaluated the safety and efficacy of the bacterial lysate, OM-85, in the primary prevention of wheezing lower respiratory tract illness.

我们报告了ORBEX试验的结果，该试验评估了细菌溶解物OM-85在预防喘息性下呼吸道疾病中的安全性和有效性。

Methods

ORBEX is a parallel-arm, double-blind, placebo-controlledtrial for the primary prevention of wheezing lower respiratory tract illness in young children at increased risk for asthma due to atopic dermatitis, parental asthma, or asthma in a blood sibling aged 4 years or older.

ORBEX是一项并行组、双盲、安慰剂对照试验，旨在评估细菌溶解物OM-85在有特应性皮炎、父母哮喘或4岁或以上血亲哮喘的儿童中预防喘息性下呼吸道疾病的一级预防效果。

Children aged 6-18 months were centrally randomly assigned (1:1) at 11 academic clinical sites with experience in recruiting young children in the USA to receive OM-85 3·5 mg or placebo orally for 10 days each month for 24 months and then followed for an additional 36 months to evaluate outcomes while they were off the study drug.

6-18个月大的儿童在11个有招募年轻儿童经验的美国学术临床站点被中心随机分配（1:1），接受OM-85 3.5 mg或安慰剂口服，每月10天，持续24个月，然后在停用研究药物后额外随访36个月以评估结果。

Identical openable capsules were used for active drug and placebo, and staff, investigators, and participants were masked to treatment assignment.

使用了相同的可打开胶囊用于活性药物和安慰剂，工作人员、调查员和参与者对治疗分配情况不知情。

Participants received usual treatment for wheezing illness as per US guidelines.

参与者按照美国指南接受了喘息性疾病的常规治疗。

Randomisation was stratified by sex, age group, family history of asthma, and clinical site.

随机分配按性别、年龄组、哮喘家族史和临床站点进行分层。

The primary outcome was the time to first wheezing lower respiratory tract illness during the 36-month observation period off the study drug analysed in the intention-to-treatpopulation, which included all randomly assigned participants.

主要结果是在停用研究药物的36个月观察期间首次发生喘息性下呼吸道疾病的时间，在意向治疗人群中进行分析，该人群包括所有随机分配的参与者。

The trial is registered with clinicaltrials.gov, NCT02148796, and is completed.

该试验已在clinicaltrials.gov上注册，编号为NCT02148796，并已完成。

Results

Between Jan 3, 2017, and Nov 30, 2020, 984 children were screened for eligibility, 162 were excluded, and 822 were randomly assigned (411 to the OM-85 intervention group and 411 to the placebo group). 492 participants were male (59·9%) and 330 (40·1%) were female and the mean age of participants was 11·8 months (SD 3·8). 681 children completed the 24-month treatment period, and 596 children completed the 36-month observation period. 132 children experienced at least one wheezing lower respiratory tract illness during the observation period; 71 (21%) of 342 in the OM-85 group and 61 (18%) of 339 in the placebo group.

在2017年1月3日至2020年11月30日期间，共有984名儿童进行了资格筛查，其中162名被排除，822名被随机分配（411名接受OM-85干预，411名接受安慰剂）。有492名参与者为男性（占59.9%），330名（占40.1%）为女性，参与者的平均年龄为11.8个月（标准差3.8）。681名儿童完成了24个月的治疗期，596名儿童完成了36个月的观察期。在观察期间，有132名儿童至少经历了一次喘息性下呼吸道疾病；OM-85组中的342名有71名（占21%），安慰剂组中的339名有61名（占18%）。

There was no significant difference between OM-85 and placebo with respect to the time to first wheezing lower respiratory tract illness (log-rank test p value 0·35; hazard ratio1·16 [95% CI 0·82-1·64]).

在第一次喘息性下呼吸道疾病发生的时间上，OM-85和安慰剂之间没有显著差异（对数秩检验的p值为0.35；风险比为1.16 [95% CI 0.82-1.64]）。

The most frequent adverse events, fevers, coughs, and colds, did not differ between groups.

最常见的不良事件，发热、咳嗽和感冒，在两组之间没有差异。

interpretation

Oral administration of OM-85 in early life did not decrease the incidenceof wheezing lower respiratory tract illness in this high-risk population.

在早期生活中口服OM-85并没有减少这一高风险人群喘息性下呼吸道疾病的发生率。

Bacterial lysates are not efficacious for the primary prevention of asthma-like symptoms during the preschool years.

细菌裂解物对于预防学龄前儿童哮喘样症状的初级预防并无效果。

funding

National Heart, Lung, and Blood Institute and OM Pharma with supplemental funding and provision of study drug and placebo from OM Pharma.

国家心肺血液研究所和OM Pharma共同资助，并由OM Pharma提供研究药物和安慰剂。