The SToP-BPD study

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The SToP-BPD study
Systemic Hydrocortisone To Prevent
Bronchopulmonary Dysplasia in preterm infants
Initiation visit
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Content

• General introduction
• Website
• Randomization procedure
• Medication schedule
• What to do at the occurence of hypertension
• Prophylactic stress medication
• Rescue therapy
• SUSAR procedure
• Discharge from level III hospital
• with study medication?
• BPD diagnosis/Oxygen reduction test

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Purpose of the study

• To investigate whether hydrocortisone, initiated
  7-14 d after birth reduces the combined outcome
  death or BPD at 36 wks PMA
• To investigate whether a potential beneficial
  effect on BPD is not at the cause of
  (inacceptable) adverse effects

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Inclusion criteria

• GA lt 30 wks and/or BW lt 1250 g
• Ventilator dependent between 7-14 days PNA
• RI (MAwP x FiO2) 3.5
• RI during gt 12 h/dy and for gt 48 uur
• Targets SpO2 85-95 / pCO2 of 5.0-7.5 kPa
• targets only for calculating RI, after inclusion
  according to local protocol!

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Exclusion criteria

• Chromosomal defects
• Major congenital malformations that
• compromise lung function (SP def., hernia)
• result in chronic ventilation (e.g. Pierre Robin
  sequence)
• Congenital cerebral malformations
• Use of steroids for improving lung function and
  respiratory status prior to inclusion

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No strict exclusion criteria

• Sepsis and/or pneumonia
• Await the effect of antibiotica 48 uur
• Hemodynamic significant ODB
• Preferable screening 7 dy and treating according
  to local protocol
• Attempt not to use indo/ibu en HC simultanuous

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Randomization

• Possible between 7-14 days PNA
• Hydrocortison or placebo 22 dys
• First dose within 24 hours after inclusion
• Web-based randomization
• Stratification according to center and GA
• Twin may be allocated to the same arm
• Procedure on the website

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Website on www.neonatologiestudies.nl (NNRN)
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eCRF

• Website
• E-learning
• Guideline
• SToP-BPD

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eCRF layout

• Screening Eligibility
• Randomization (twins)
• Visits
• Daily reports
• Conditions
• Range
• Validation
• Derivation

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Print out Daily reports
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Medication
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HC course

• Hydrocortison Pharmachemie (100 mg/ml)
• Cumul. dose 72,5 mg/kg (2.5 mg/kg dexa)
• 5 mg/kg/d in 4xday during 7 dys
• 3,75 mg/kg/d in 3xday during 5 dys
• 2,5 mg/kg/d in 2xday during 5 dys
• -1,25 mg/kg/d in 1xday during 5 dys
• Total duration 22 days

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Placebo course

• ACE pharmaceuticals Zeewolde, NL
• Mannitol as base (pH en Osmol identical to HC)
• Same concentration/dose as HC
• On the shelf stable for 3 years

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Study medication

• Transported via AMC, delivered in badges of 10
  pieces
• Issue locally by the pharmacy
• (per patient or per badge)
• Stock will be automattically suplemented
  according to use
• Medication kit contains of 23 vials

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Study medication

• After randomization a medication order can be
  printed from the website

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Study medication

• Preparation protocol
• Diluent from own stock
• Preparation of medication per dag
• Medication recorded on drug accountability form

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Medication schedule
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Details medication

• Occurring of hypertension
• Prophylactic stress medication
• Go to website/protocol

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• Rescue therapy

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Treatment failure of vroege rescue

• Reason for considering open label rescue
• deterioration with RIgt10 for gt6 uur
• no improvement (RIlt10) and
• At least 10 dys study medication
• Attempt to extubate failed lt 24 hrs
• Rescue with HC according to study schedule and
  stop study medication

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Late rescue treatment

• Patient still ventilator dependent after 22 d
• Attempt to extubate failed
• Late rescue possible with HC according to study
  protocol

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Safety and reportingAE/SAE/SUSAR

• AE Any undesirable experience occurring to a
  subject duringthis trial, whether or not
  considered related to the investigational.
• An AE is a SAE if
• Resulted in death
• Life-threatening
• Required (prolongation of existing)
  hospitalisation
• Persistent or significant disability/incapacity
• Another important medical condition

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Context-specific SAEs

• Study population at high risk of serious
  complications,
• inherent to their vulnerable condition
• unrelated to the intervention which is under
  evaluation
• Endpoints of the study in the CRF
• Immediate reporting of these complications will
  not enhance the safety of this trial
• Reporting of these events to the DMC and METC on
  a annual basis.

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Suspected (Unexpected) Serious Adverse Reactions
(SUSAR)

• SUSAR adverse reactions, of which the nature,
  or severity, is not consistent with the
  applicable product information or the
  context-specific SAEs as listed above.
• Reporting lt 24 hrs on AE page of CRF and by
  telephone to the PI

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Web-based Alert procedure

• Alert Procedure (automated email to
  stop-bpd_at_amc.nl) should be used with
• Death
• Simultanuous treatment of indomethacine/ibuprofen
  and study medication
• Occurrence of solitair gastointestinal
  perforation
• Occurence of hypertension, as defined in the
  protocol
• Use of open label hydrocortisone
• Reporting should be done lt 72 hrs of the
  occurence of the event.

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Discharge from level III hospital

• Letter for general pediatrician on the website

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Oxygen reduction test

• Criteria only O2 defined
• Depending on saturation targets or other
  diseases
• Practical guideline on the website

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Logistics oxygen reduction test

• Local?
• Familiair with reduction test
• Training of local pediatricians
• Regional?
• Research nurse?
• Recording?

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• Vragen?