Efficacy of Methylprednisolone Pulses in Neuroendocrine Celles Hyperplasia of Infancy : An Early Phase Study

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)

For the research needs,

• CT scan and Echocardiography will be done at inclusion if not performed in the past 3 months
• QoL questionnaires will be performed at inclusion, M6, M12 and M18
• Dipstick for sugar will be performed at M6, M9, M12, M15, M18 (in addition to M0 - M5 according to the standard of care)

Inclusion criteria

• 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

Exclusion criteria

• 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)
• Diabetes
• 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)