the stop-bpd study systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants...
TRANSCRIPT
The SToP-BPD study
Systemic Hydrocortisone To Prevent Bronchopulmonary
Dysplasia in preterm infants
Initiation visit
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
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
Inclusion criteria
• GA < 30 wks and/or BW < 1250 g• Ventilator dependent between 7-14 days PNA• RI (MAwP x FiO2) ≥ 3.5• RI during > 12 h/dy and for > 48 uur• Targets SpO2 85-95% / pCO2 of 5.0-7.5 kPa
– targets only for calculating RI, after inclusion according to local protocol!
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
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
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
eCRF
• Website
• E-learning
• Guideline
SToP-BPD
eCRF layout
• Screening & Eligibility• Randomization (twins) • Visits
– Daily reports
• Conditions– Range– Validation– Derivation
Print out Daily reports
Medication
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
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
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
Study medication
• After randomization a medication order can be printed from the website
Study medication
• Preparation protocol
• Diluent from own stock
• Preparation of medication per dag
• Medication recorded on drug accountability form
Medication schedule
Details medication
• Occurring of hypertension
• Prophylactic stress medication
Go to website/protocol
Rescue therapy
Treatment failure of vroege rescue
• Reason for considering open label rescue:– deterioration with RI>10 for >6 uur– no improvement (RI<10) and:
• At least 10 dys study medication• Attempt to extubate failed < 24 hrs
• Rescue with HC according to study schedule and stop study medication
Late rescue treatment
• Patient still ventilator dependent after 22 d
• Attempt to extubate failed
• Late rescue possible with HC according to study protocol
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
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.
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 < 24 hrs on AE page of CRF
and by telephone to the PI
Web-based Alert procedure
Alert Procedure (automated email to [email protected]) 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 < 72 hrs of the occurence of the event.
Discharge from level III hospital
• Letter for general pediatrician on the website
Oxygen reduction test
• Criteria: only O2 defined
• Depending on saturation targets or other diseases
• Practical guideline on the website
Logistics oxygen reduction test
• Local?– Familiair with reduction test– Training of local pediatricians
• Regional?– Research nurse?– Recording?
Vragen?