Miles Caitlin, Katz Tamarah, Grunert Jodi, Ford Kristyn, Hall Carla, Hawthorn Charlotte, See Denise Wong, McMahon Mylie, Vass Hannah, Watkins Sarah, Zanardo Gemma, Brookes Isabella, Handley Siobhan, Woodward Talia, Wademan Jasmin, Cameron Bella, King Sophie, Nixon Gillian M, Davidson Zoe
Nutrition and Dietetics, Monash Children's Hospital, Clayton, Victoria, Australia
Respiratory Medicine, Monash Children's Hospital, Clayton, Victoria, Australia.
BMJ Open. 2025 Jul 30;15(7):e097071. doi: 10.1136/bmjopen-2024-097071.
Cystic fibrosis (CF) is a genetic condition of impaired membrane electrolyte transport and is characterised by defects in the production and function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Ground-breaking CFTR modulator therapy has resulted in a notable shift in the clinical presentation and progressive nature of CF, across both pulmonary and extrapulmonary systems. Access to CFTR modulator therapies in people with CF is occurring in a staged, descending age process, with clinical trials focusing primarily on safety and efficacy. There is a lack of robust, real-world longitudinal data on CFTR modulator therapy in infants and young children where extrapulmonary outcomes such as growth, micronutrient status and pancreatic function are the key focus.
Pancreatic, nutritional and clinical outcomes in children 0-5 years with CF during the first 2 years of CFTR modulator therapy (PaNC) is a prospective cohort study involving all eight tertiary paediatric CF centres in Australia. Infants and children 4 months to 5 years of age who are eligible for elexacaftor/tezacaftor/ivacaftor (ETI) or ivacaftor (IVA) meet the inclusion criteria for PaNC, with a total eligible cohort of 303 children at the commencement of recruitment. The primary outcomes are change in weight-for-length/body mass index z score and change in serum micronutrient status, at 6-12 monthly intervals, during the first 2 years of treatment with ETI or IVA. Secondary outcomes include change in exocrine pancreatic function, measured by faecal elastase-1, change in the use and dose of pancreatic enzyme replacement therapy, nutritional and gastrointestinal therapies and change in sweat chloride levels. Linear mixed modelling will be used to analyse primary and secondary endpoints. This protocol is reported in accordance with 'The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement' reporting guidelines.
Overarching governance and ethics approval has been granted by Monash Health Human Research Ethics Committee, in addition to all eight sites receiving site-specific authorisation approvals prior to the commencement of recruitment. Opportunities for CF consumers to be involved in targeted dissemination plans will be initiated via CF Australia at the completion of the study period. Additionally, a summary of non-identifiable results will be provided to CF consumers and CF healthcare providers via scientific and lay conferences and via peer-reviewed journals.
ACTRN12624001185550; Pre-results.
囊性纤维化（CF）是一种膜电解质转运受损的遗传性疾病，其特征是囊性纤维化跨膜传导调节因子（CFTR）蛋白的产生和功能存在缺陷。开创性的CFTR调节剂疗法已导致CF在肺和肺外系统的临床表现及进展性质发生显著转变。CF患者获得CFTR调节剂疗法的过程是分阶段、年龄递减的，临床试验主要关注安全性和有效性。对于婴幼儿，缺乏关于CFTR调节剂疗法的可靠的真实世界纵向数据，而生长、微量营养素状况和胰腺功能等肺外结局是关键关注点。
CFTR调节剂治疗头两年CF患儿的胰腺、营养及临床结局（PaNC）是一项前瞻性队列研究，涉及澳大利亚所有八家三级儿科CF中心。符合 eligafactor/tezacaftor/ivacaftor（ETI）或ivacaftor（IVA）治疗条件的4个月至5岁婴幼儿符合PaNC纳入标准，招募开始时共有303名符合条件的儿童。主要结局是在接受ETI或IVA治疗的头两年中，每隔6至12个月测量的身长别体重/体重指数z评分变化和血清微量营养素状况变化。次要结局包括通过粪便弹性蛋白酶-1测量的外分泌胰腺功能变化、胰腺酶替代疗法的使用和剂量变化、营养及胃肠道疗法变化以及汗液氯化物水平变化。将使用线性混合模型分析主要和次要终点。本方案按照“加强流行病学观察性研究报告（STROBE）声明”报告指南进行报告。
莫纳什健康人类研究伦理委员会已给予总体治理和伦理批准，此外所有八个研究点在招募开始前均获得了特定研究点的授权批准。研究结束后，将通过澳大利亚囊性纤维化协会为CF患者提供参与定向传播计划的机会。此外，将通过科学会议和大众会议以及同行评审期刊向CF患者和CF医疗服务提供者提供不可识别结果的摘要。
ACTRN12624001185550；结果前。
