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;334-337

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 7-14 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 www.neonatologiestudies.nl

(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 email to stop-bpd@amc.nl) should be used when:

• 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 O2

• Dependent on saturation targets or other conditions

• Practical guideline on the website

Questions?