NHSBT/MRC Clinical Studies Unit
Staying true to the protocol
Vidheya Venkatesh
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
The Delegation Log
• GCP training• CVs• Delineation of roles: consenting training
NHSBT/MRC Clinical Studies Unit
The Screening log
• Removal of Patient identifiable data• Remember to send monthly
NHSBT/MRC Clinical Studies Unit
Pre randomisation
• Excluding major bleed• Documenting scan HVP
NHSBT Clinical Trials UnitNHSBT CTU
NHSBT/MRC Clinical Studies Unit
• Major/life-threatening congenital malformations
• Recent major haemorrhage within the last 72 hours
• All fetal intracranial haemorrhages
• Known immune thrombocytopenia
• Neonates unlikely to survive
• Neonates not given parenteral vitamin K
Who is excluded?
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
Who is not excluded?
• Previous thrombocytopenia• Previous transfusions• 72 hours after bleed if not actively bleeding• Older babies
NHSBT/MRC Clinical Studies Unit
Passing your data monitoring visit
NHSBT/MRC Clinical Studies Unit
When platelets <100x109/L
Parents will be
counselled
Written, informed
consent will be obtained
Documented in the clinical
notes
Three copies signed:• For parents• For the clinical
notes with Parent Information Sheet
• For the study file
When platelets <50x109/L
Parents will be approached for consideration of immediate
study participation.
Documenting consent
Document on PlaNeT-2 log book
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
Documenting randomisation
NHSBT/MRC Clinical Studies Unit
NHSBT/MRC Clinical Studies Unit
• What is a protocol deviation?• When not to give platelets
Keeping in the right arm
NHSBT Clinical Trials UnitNHSBT CTU
NHSBT/MRC Clinical Studies Unit
Platelet Transfusion Data (F8)
Necrotising enterocolitis (NEC) /Sepsis Form (F9)
Discontinuation of Treatment Allocation (F10)
Major/Severe Bleed (F13)
Serious Adverse Event (F14)
Serious Platelet Transfusion Related Adverse Event (F15)
The Paperwork
F9
F13
F10
F14
F15
F8
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
F5 – Bleeding Assessment Tool (BAT)
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
Major bleed reporting
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
• All new major bleeding events will be reported to the CSU without disclosing allocation arm.
• Each report will be forwarded to the Independent Data Monitoring Committee for review as soon as it is received at the CSU.
• In cases of uncertainty the local team may contact one of the CIs or neonatal medical experts.
MAJOR BLEED FORMWithin one working day of becoming aware of an Major Bleed, please fax a completed Major Bleed form to the NHSBT/MRC
CSUFax: 01223 588136
PlaNeT-2: Major/Severe bleed form
NHSBT/MRC Clinical Studies Unit
Grade 1 – Minor HaemorrhageAny bleed from the
· skin, umbilical cord, skin around stoma, surgical scar, mucosa.· Any pink frothy or old bleed from the ET tube. · H1 haemorrhage on cranial US (Germinal Layer Haemorrhage, GLH)
Grade 2 – Moderate HaemorrhageAny frank bleed from
• the stoma • macroscopic haematuria, • IVH (H2 or H3) without dilatation (V0), • Acute fresh bleed through ETT without ventilatory changes
Grade 3 – Major Haemorrhage any:• Frank Rectal • Acute fresh bleed through ETT with ventilatory change. • Intracranial bleed An intracranial bleed is defined as a major bleed if any of the following apply: Neurosurgical
intervention is required; Scans show a midline shift; Clinical signs and symptoms of neurolgical deficit with significant derangement of laboratory investigations
• Major IVH is defined as H2 or H3 with ventricular dilatation (V1); H1, H2, H3 with parenchymal involvement (P3) ; Any evolution of intracranial haemorrhage to H2V1, H3V1, or (H1, H2, H3) with parenchymal involvement (P3)
Grade 4 – Severe Haemorrhage• Shock defined as life threatening major bleed associated with hypotension, hyopovolaemia or any other
haemodynamic instability and/or bleeding requiring volume boluses, red cell transfusion in the same 24 hours, fatal major bleeding
Modified WHO Bleeding Assessment Score
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NHSBT/MRC Clinical Studies Unit
Safety reporting
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NHSBT/MRC Clinical Studies Unit
F14 – Serious Adverse Event
NHSBT CTU
NHSBT/MRC Clinical Studies UnitSAE NOTIFICATION
Within one working day of becoming aware of an SAE, please fax a completed SAE form to the NHSBT/MRC CSU
Fax: 01223 588136
• in death• is life-threatening • requires hospitalisation or prolongation of existing
hospitalisation (including readmission within 28 study days if discharged home earlier)
• there is a likelihood of persistent or significant disability or incapacity
A SAE is an adverse event that results:
PlaNeT-2: Serious Adverse Event (SAE)
NHSBT/MRC Clinical Studies Unit
Adverse events
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
• Necrotising enterocolitis ≥ Stage 2 defined as per Bells Criteria (Bell et al,1978)
• Sepsis: culture positive sepsis or culture negative sepsis where a course of at least 5 days of antibiotics is to be administered for proven or clinically-suspected sepsis.
• All episodes of NEC and sepsis must be recorded on the adverse event form
• A listing of adverse events will be reported six monthly to the Independent Data Monitoring Committee.
Defining NEC/Sepsis
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
Primary outcome: 28 days
28 day scan
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
End of Study
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
F11 – Cranial USS at the end of study
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
• Inform the local PlaNeT-2 team if neonate transferred out of recruiting unit
• Use transfer pack
• Receiving hospital should:• Collect information as required by the protocol thereafter until 38 weeks
CGA or discharge.
PlaNeT-2: Transfer out of recruiting unit
NHSBT CTU
NHSBT/MRC Clinical Studies Unit
Thank you!
NHSBT CTU