Oral Bacterial Lysate to Prevent Persistent Wheeze in Infants After Severe Bronchiolitis; a Randomised Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 173
- 试验地点
- 3
- 主要终点
- Number of a wheeze episodes by 12 months
研究概览
简要总结
Bronchiolitis is a common viral infection of the small airways of infants and some affected infants will require hospital admission. Severe bronchiolitis is a marker for greatly increased risk of developing both preschool wheeze and subsequent school age asthma. Since epidemiological studies suggest that exposure to microbial products protects against preschool wheeze, lysates of bacteria may prevent the development of wheeze after bronchiolitis, with long-term beneficial consequences.
BLIPA is a phase 2b, randomised, double blind, placebo-controlled study, investigating the efficacy superiority of bacterial lysate (Broncho Vaxom) capsules over placebo, in reducing wheeze in infants after severe bronchiolitis. The primary end point of the study to establish whether there is superiority of oral Broncho-Vaxom over placebo in reducing the number of parent-reported wheeze episodes by 12 months post IMP/placebo initiation. The study aims to test bacterial lysate capsules (3.5mg over 12-24 months) for safety, efficacy, and to advance mechanistic understanding of its action.
详细描述
The BLIPA study aims to investigate the following research questions:
- In children hospitalised with bronchiolitis, does Oral Broncho-Vaxom reduce incidence of parent-reported wheeze during 12 months post IMP initiation after a hospital admission for bronchiolitis.
- Does oral BV reduces the risk of wheeze after bronchiolitis by modulating T cell and Dendritic cells (DC) maturation and altering the gut and airway microbiota. (mechanistic hypothesis)
The BLIPA study will combine the results of two multi-centre, randomised trials with similar but separate protocols: BLIPA-United Kingdom (UK), with recruitment in London, Southampton, Cheshire and Aberdeen and BLIPA-Australia, with recruitment in Brisbane, Gold Coast, Melbourne, Darwin and Sydney.
BLIPA-UK is funded in the UK by the NIHR (National Institute for Health and Care Research). BLIPA-Australia is funded in Australia by the International Clinical Trial Collaboration (ICTC). ICTC supports Australian researchers to conduct clinical trial research in collaboration with international researchers.
The total study duration is 74 months. The primary clinical objective is to recruit a population of eligible participants, to randomise them to oral Broncho Vaxom (3.5mg) or placebo, to be taken daily for 10 days a month over 12-24 months, follow up for 12-24 months and compare primary and secondary outcomes between trial arms. Parents or guardians of children, clinicians involved in their care and trial staff will be blinded to the treatment arm. Recruitment will be for 18 months and children's outcomes will be assessed for 24 months following initiation of Investigational Medicinal Product (IMP) or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Parents or guardians will be blind to treatment allocation, as will the entire site study team involved in the management of the study, including the Chief Investigator (CI), PIs, sub-investigators, study nurses, and site coordinators. Trial Steering Committee (TSC) members will remain blind. The progress and safety of the study will be assessed by the Data Monitoring Committee (DMC). The DMC will therefore not be blinded. The main study trial manager (PCTU) and trial monitors will be blinded. The Sponsor's Joint Research Management Office (JRMO) including the JRMO monitor(s) will unblind themselves to specific patients in order to report SUSARs to the Medicines and Healthcare products Regulatory Agency (MHRA). The study pharmacist will be blinded, and the study pharmacy file will contain blinded documents, please see pharmacy manual. The treatment allocation list will be available from the PCTU or their designate (Sealed Envelope) on request should the need arise.
入排标准
- 年龄范围
- 2 Weeks 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parent/Guardian able to provide written informed consent
- •Within 6 weeks of discharge from hospital for bronchiolitis
- •Child aged ≥2 weeks and ≤12 months at the time of consent to study
- •A diagnosis of Bronchiolitis requiring a hospital admission (defined as more than 4 hours in hospital)
- •Contactable for regular follow up by the research team
排除标准
- •Any previous hospital attendance for bronchiolitis
- •More than one episode of healthcare professional-diagnosed wheeze prior to index bronchiolitis episode
- •Premature gestational age less than 37 weeks
- •Any severe chronic condition such as cystic fibrosis, sickle cell disease, severe developmental delay, immunodeficiency, or anything that has a significant impact on the respiratory tract (such as need for non-invasive ventilation) or increases vulnerability to respiratory tract infections.
- •History of clinically significant neonatal disease (e.g. neonatal pneumonia, congenital lung abnormality, neonatal chronic lung disease)
- •Genetic conditions that affect the immune system (e.g. Down's syndrome/Trisomy 21)
- •Current regular oral montelukast or inhaled corticosteroid therapy or inhaled salbutamol therapy
- •Current regular treatment with immunomodulatory drugs (e.g oral steroids)
- •Known allergy or previous intolerance to study medication.
- •Currently enrolled to another Randomised Clinical Trial. (Unless prior approval is given by Principal Investigator)
- •Sibling of a BLIPA participant (of the same household or family)
研究组 & 干预措施
Placebo control
Matched placebo administered daily for 10 days per month for 12-24 months
干预措施: Bacterial Lysate (Drug)
Active intervention
Oral Broncho-Vaxom (3.5mg) administered daily for 10 days per month for 12-24 months
干预措施: Bacterial Lysate (Drug)
结局指标
主要结局
Number of a wheeze episodes by 12 months
时间窗: 12 months
To establish whether there is superiority of oral Broncho-Vaxom over placebo in the reduction of parent reported wheeze episodes by 12 months post IMP/placebo initiation
次要结局
- Incidence of adverse events (AEs) for the treatment group between 0-24 months(0-24 months)
- Incidence of serious adverse events (SAEs) for the treatment group between 0-24 months(0-24 months)
- Incidence of Suspected unexpected serious adverse reactions (SUSARs) for the treatment group between 0-24 months(0-24 months)
- To establish whether there is a difference between treatment with Broncho-Vaxom or placebo in healthcare professional confirmed wheeze episodes by 12 months post IMP initiation.(12 months)
- Occurrence of hospital admissions for wheeze-related illness by 12 months.(12 months)
- Occurrence of unscheduled medical attendance for wheeze-related illness by 12 months(12 months)
- Presence of wheeze diagnosis by 12 months(12 months)
- Time to first wheeze episode by 12 months(0-12 months)
- Incidence of adverse events (AEs) for the treatment group by 12 months(12 months)
- Incidence of Suspected unexpected serious adverse reactions (SUSARs) for the treatment group by 12 months(12 months)
- Duration of wheeze by 12 months(12 months)
- Hospital admissions for respiratory related illness (rate[episodes per child-month] and yes/no) by 12 months(12 months)
- Development of eczema by 12 months(12 months)
- Incidence of serious adverse events (SAEs) for the treatment group between 0-24 months(0-24 months)
- Development of Dr-diagnosed food allergy by 12 months(12 months)
- Incidence of serious adverse events (SAEs) for the treatment group by 12 months(12 months)
- Incidence of adverse events (AEs) for the treatment group between 0-24 months(0-24 months)
- Occurrence of all-cause acute respiratory infection by 12 months(12 months)
- Quality of life confirmed by Warwick Child Health and Morbidity by 12 months(12 months)
- Number of courses of oral corticosteroids for wheeze by 12 months(12 months)
- Incidence of Suspected unexpected serious adverse reactions (SUSARs) for the treatment group between 0-24 months(0-24 months)