Efficacy of Methylprednisolone Pulses in Neuroendocrine Celles Hyperplasia of Infancy : An Early Phase Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of children still requiring oxygen therapy
研究概览
简要总结
Childhood interstitial lung diseases (chILD) are a heterogeneous group of rare and severe disorders with an estimated prevalence of 1/100,000. Among them, neuroendocrine cells hyperplasia of infancy (NEHI), also called persistent tachypnoea of infancy (PTI), is one of the most common aetiology (up to 16% of the cases). NEHI involves young infants (median age at onset 3 to 6 months) with tachypnoea, hypoxemia, crackles, retractions, failure to thrive and specific localizations of ground glass opacities (GGO) on chest CT-scan (paramediastinal areas and anterior lobes (right middle lobe and lingula). At diagnosis, most patients (50 to 100%) require oxygen supplementation that usually lasts for months to years, sometimes associated with nutritional support with eventual enteral nutrition. NEHI is believed to be related to an increased number of neuroendocrine cells in airway epithelial area. These cells are abundant in foetal life, when they play a role in regulating the lung development and decrease before birth.
There is no specific treatment for NEHI. The main treatment of chILD is corticosteroids. However, in NEHI, their efficacy is matter of debate. There is only a few NEHI cases series or cohorts all over the world, accounting for a maximum of 500 reported cases within only retrospective studies. Among them, United States and Argentina teams report supportive care only (oxygen therapy and nutritional support) whereas other teams, like the French ones largely uses IV corticosteroid pulses.
Unlike the majority of chILD, NEHI prognosis is usually good. However, at school-age, 26% of the patients remain symptomatic or have an abnormal lung function. Moreover, oxygen therapy significantly affects quality of life (QoL) of the children with ILD (-10.43/100 points, p=0.02) but also QoL and mood of their parents (unpublished data).
The present study hypothesis that corticosteroids are associated with a reduction of the length of oxygen support in infants with NEHI.
详细描述
This study aims at assessing the beneficial effect of IV methylprednisolone pulses on oxygen therapy in infants with NEHI. It applies to all hypoxic NEHI patients aged below 12 months and followed in one of the centres of the RespiRare network. 18 patients will be recruited.
CORTICO-NEHI is designed as an early phase study following an A'Hern's Single Stage Phase II design.
All the patients are included in a single group receiving as a standard of care a maximum of 6 IV pulses of 3 days each.
12 visits will be performed as a standard of care:
- Screening visit (M-1 at maximum) :follow-up routine visit, (usually the hospitalization for NEHI diagnosis). If the patient is eligible, parents are informed of the study and an informed note is given. Information on the study protocol is given to obtain their written consent as soon as possible, and at the latest at the inclusion.
- Inclusion (M0) : After checking of the inclusion criteria and the absence of exclusion criteria, information and collection of parental consent. Following these investigations, the patient's first IV methylprednisolone pulse (D1) is administrated within the limit of 10 days.
- Treatment visits (M0 - M5): During a hospitalization, 6 pulses are performed at a 4 weeks interval (+/- 10 days). Each pulse is a 3-days-6h-perfusions of Methylprednisolone (500mg and 120mg) 10mg/kg/day diluted in 50ml of saline under supervision of SpO2, heart rate, blood pressure / 30min. If oxygen can be stopped (2 oxymetries with a 1-week interval +/- 10 days): The endpoint is reached and the methylprednisolone pulses are definitively stopped.
- Follow-up visits (M6, M9, M12, M15 and M18)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infant aged under 12 months
- •NEHI diagnosis based on:
- •The recently validated clinical Liptzin score ≥7/10 associated with a suggestive thoracic CT pattern with ground glass opacities confined to middle lobe, lingula, and paramediastinal lung areas OR
- •a clinical and thoracic CT suspicion and a lung biopsy showing an increased number of neuroendocrine cells in the epithelial airways area (at least one bronchiole with at least 10% of neuroendocrine cells)
- •Oxygen requirement (awake and/or asleep) based on the usual pediatric recommendations (see section 4.1.1)
- •Followed in one of the RespiRare participating centers
- •Written informed consent of the holder(s) of its legal representative at the inclusion
排除标准
- •Other cause of chILD assessed by lab biology tests, genetic analysis for surfactant genes (if available), bronchoalveolar lavage, and/or lung biopsy.
- •Patient treated with IV methylprednisolone pulses before (any time)
- •Uncontrolled arterial hypertension
- •Absence of Health care insurance
- •Ongoing infection
- •Immunization with a live attenuated vaccine within the past two weeks
- •Long term treatment with Azithromycin and/or Hydroxychloroquine
- •Patients already included in an interventional study (RIPH1, clinical investigation or clinical trial)
研究组 & 干预措施
IV Methylprednisolone pulses
干预措施: IV Methylprednisolone pulses (Drug)
结局指标
主要结局
Number of children still requiring oxygen therapy
时间窗: Month 18
To evaluate the efficacy on oxygen therapy need of a 6 months methylprednisolone pulses in NEHI patients at M18.
次要结局
- The number of patients with a normal respiratory rate(Month 18)
- Time to achieve the oxygen therapy weaning(Month 18)
- ChILD healing (reduction of severity) over time(Between Month 0 and Month 18)
- Parents QoL(Month 0 and Month 18)
- Number of antibiotic courses for an infectious lung exacerbation(Between Month 0 and Month 18)
- To compare the family impact PedsQL questionnaire to the newly described chILD-PQoL questionnaire(Month 0, Month 6, Month 12, Month 18)
- The number of patients requiring continuous oxygen therapy (meaning sleep and awake oxygen therapy by opposition to sleep oxygen only) over time(Month 18)
- The number of patients requiring only sleep oxygen over time(Month 18)
- Patient's QoL(Month 0 and Month 18)
- Impact of NEHI on feeding and growth status(Between Month 0 and Month 18)
- Safety of methylprednisolone pulses(At Month 6)
- To study thoracic CT-scan evolution(at Month 6 and Month 18)