The SToP-BPD study Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants Clinical lesson Oct 2011

History of steroids in neonatology

The Evidence EC Eichenwald, AR Stark; Arch. Dis. Child. Fetal Neonatal Ed. 2007;92;

Furthermore… Consequence of publications on adverse neurological sequelae: late and low doses dexa Current policy Amsterdam: 1.4 mg/kg cumulative dose

Hydrocortison Netherlands: 4 centra administer hydrocortison, 6 dexa in low doses HC: No prospective studies on risk:benefit ratio Retrospective studies –No adverse effects neurological outcome (no placebogroup) –Case control compared to dexa no decreased effect fot the lungs

Equipoise! Therefore, it is time for a nwe trial

Objective of the study Investigate is hydrocortisone, initiated d after birth, reduces the combined outcome of death or BPD at 36 wks PMA Investigate if a possible beneficial effect on BPD is not with (unacceptable) increased adverse effects

Inclusion criteria GA < 30 wks and/or BW < 1250 g Ventilator dependent between 7-14 d PNA RI (MAwP x FiO2) ≥ 3.5

Exclusion criteria Chromosomal abnormalities Congenital pulmonary abnormalities Congenital neurological abnormalities Steroid treatment prior to inclusion with the purpose to improve the pulmonary function –NB not hypotension

Randomization Possible between 7-14 d PNA Hydrocortison or placebo 22 dg First dose within 24 hr after inclusion Twins can be allocated to the same group –Procedure on the website

Website at (NNRN)

Medication HC course –Hydrocortisone Cumul. dose 72,5 mg/kg (=2.5 mg/kg dexa): 5 mg/kg/d in 4 times for 7 d 3,75 mg/kg/d in 3 times for 5 d 2,5 mg/kg/d in 2 times for 5 d 1,25 mg/kg/d in 1 once daily for 5 d Placebo mannitol as base (pH and Osmol HC) Medication kit contains of 23 vials Totale duration 22 days

Medication program

Study medication Pharmacy prepares medication PDMS configuration Medication per day prepared

Rescue therapy

Treatment failure of vroege rescue Reason for consideration open label rescue: –deterioration with RI>10 for >6 uur –No improvement (RI<10) and: At least 10 dys study medication Failure extubation attempt < 24 hr before starting rescue Rescue with HC according to study schedule and stop study medications

Late rescue treatment Patient still ventilator dependent after 22 d Failed extubation attempt Late rescue possible with HC according to study protocol

Documents for the Nurses Summary (also in French)

Print out Daily reports

Web-based Alert procedure Alert Procedure (automated to should be used Occurrence of a SUSAR Death Simultanousely using indomethacine/ibuprofen and study medication Occurrence of an solitary intestinal perforation Occurrence of hypertension, as defined in protocol Use of open label hydrocortisone Reporting should be done < 72 hr of becoming aware ot the event.

Discharge from level III center Letter for paediatrician on the website (also in French)

Oxygen reduction test Criteria: only defined by O 2 Dependent on saturation targets or other conditions Practical guideline on the website

Questions?