Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants.

Background:

Randomised controlled trials (RCTs) have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of bronchopulmonary dysplasia (BPD). However, there are concerns that its use may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no RCT has investigated its efficacy when administered after the first week of life to ventilated preterm infants.



Objective:

To establish the efficacy of hydrocortisone given after one week of life to reduce the incidence of the combined outcome death or BPD in chronically ventilated preterm infants.



Study design:

Randomised double blind placebo controlled multicenter study.



Study population:

Very low birth weight infants (GA < 30weeks and/or BW < 1250grams), ventilator dependent at a postnatal age of 7 – 14 days.



Intervention:

Administration of hydrocortisone or placebo during a 22 day tapering schedule.



Outcome parameters:

Primary outcome measure is survival free of BPD at 36 weeks postmenstrual age (PMA). Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age (CGA).



Burden, benefit and risks associated with participation; group relatedness:

Burden: All infants participating in (either treatment arm of) the study are subjected to routine neonatal intensive care. The administration of the study intervention itself (hydrocortisone or placebo administration) does not pose an extra burden on the patients. This study does not require extra investigations or interventions.

Benefit and risks: Hydrocortisone may facilitate extubation and thereby reduce the total duration of mechanical ventilation. In addition, hydrocortisone may reduce the incidence of BPD. Both these beneficial effects may improve neurodevelopmental outcome. On the other hand, use of hydrocortisone may increase the risk for hyperglycemia, hypertension, systemic infection, gastrointestinal perforation and a delay in neurodevelopment. However, gastrointestinal perforation and delayed neurodevelopment have only been reported in studies administering corticosteroids in the first week of life and/or during combinations with other medication. In this study the risk of gastrointestinal perforation and delayed neurodevelopment may be reduced because hydrocortisone will be administered after the first week of life and will not be combined with other drugs that are known to increase the risk for these adverse effects. Infants assigned to the placebo group will not benefit from the aforementioned possible beneficial effects nor be subjected to the possible adverse effect of hydrocortisone.

Group relatedness: BPD is a complication occurring exclusively in preterm infants. Any intervention aiming to reduce the risk of this complication therefore needs to be studied in this specific population at risk.

Is hydrocortisone safe and effective in reducing the incidence of the combined outcome death or BPD at 36 weeks PMA in chronically ventilated preterm infants, as compared to placebo.

Inclusion 3 years;

Follow-up 2 years.

Administration of hydrocortisone or placebo during a 22 day tapering schedule.