nhsbt/mrc clinical studies unit nhsbt clinical studies unit platelets for neonatal transfusion study...

NHSBT/MRC Clinical Studies UnitNHSBT Clinical Studies Unit NHSBT Clinical Studies Unit

Platelets for Neonatal Transfusion Study 2 (PlaNeT-2):

A randomised controlled trial of platelet transfusion thresholds

NHSBT/MRC Clinical Studies UnitNHSBT Clinical Studies Unit

Current national transfusion guidance based on

consensus rather than evidence British Committee for Standards in Haematology (2004)

United Kingdom Blood Services (2007)

Survey in the UK showed wide variation in platelet

transfusion practice Chaudhary and Clarke (2008)

Neonatal Thrombocytopenia: Current Practice


Platelets for Neonatal Transfusion - Study 2

PlaNeT-2


PlaNeT-2: Study design (I)

Two-stage, randomised, parallel group, superiority trial.

Aim: to compare two different platelet count thresholds for

prophylactic platelet transfusion to preterm neonates.

Primary Outcome:• Proportion of patients who either die or experience a major

bleed up to and including study day 28.


PlaNeT-2: Study design (II)

Secondary Outcomes:• Proportion of neonates surviving to home following a

major bleed• Mortality prior to day 28• Major bleeds by day 28 • Platelets transfused to study day 28• Length of hospital stay• Transfusion-related adverse events • Neuro-developmental outcome


PlaNeT-2: Choosing platelet thresholds

Last RCT done by Andrew et al (1993) assessed

50-150x109/L vs. >150x109/L

PlaNeT-1 (2009):

• Most transfusions given at platelets 10–50x109/L.

• 50th and 90th centile pre-transfusion platelet counts

27 and 48x109/L.

• 42% transfusions <25x109/L and 92% <50x109/L


PlaNeT-2: Platelet thresholds

• Arm A Standard: transfuse platelets at <25x109/L

(330 neonates)

• Arm B Intervention: transfuse platelets at <50x109/L

(330 neonates)

Dose: 15 ml/kg


PlaNeT-2: Additional platelet transfusions

May be considered under the following circumstances:

• Therapeutically to treat moderate, major or severe bleeding but not for minor bleeding.

• Prior to planned invasive procedures as below only – Suprapubic aspiration

– Lumbar puncture

– Major surgery where haemostasis may be critical to outcome.


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


• Admission to a participating NICU (includes postnatal transfers)

• <34 weeks GA at birth

• Platelet count of <50 x109/L

• Cranial ultrasound scan: undertaken <6 hours before randomisation to exclude recent major IVH

PlaNeT-2: Inclusion criteria


• 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

PlaNeT-2: Exclusion criteria


When platelets <100x109/L

When platelets <50x109/L

PlaNeT-2: Consent

Document on PlaNeT-2 log book


PlaNeT-2: Randomisation

When the consent is signed and platelets <50x109/L:

Pre-randomisation

Platelet transfusion information

(FA)

Pre-randomisation

form (F1)

Eligibility for randomisation

(F2)

Current medical

conditions & previous major

bleeds (F3)

Randomisation (F4)


FA – Platelet transfusion information


F1 – Pre-randomisation


F2 – Eligibility for randomisation


F3 – Current medical conditionsAnd previous major bleeds


F4 – Randomisation


PlaNeT-2: Data collection (I)


F5 – Bleeding Assessment Tool (BAT)


F6 – Daily Platelet Count


F7 – Weekly Data Collection


PlaNeT-2: Data collection (II)

F9

F13

F10

F14

F15

F8


F8 – Platelet Transfusion Data


• 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.

PlaNeT-2: NEC/Sepsis form


F9 – NEC/Sepsis form


F10 – Discontinuation of Treatment Allocation


• 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


F13 – Major/Severe Bleed

NHSBT/MRC Clinical Studies UnitNHSBT Clinical Studies Unit SAE 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)


F14 – Serious Adverse Event


Data collected on serious transfusion related adverse reactions/events will be based on current definitions used by hospitals reporting to UK national haemovigilance reporting schemes (SHOT and MHRA).

These definitions cover the following: Incorrect blood component transfused Acute transfusion reactions Transfusion Related Acute Lung Injury (TRALI) Transfusion transmitted infections, including bacterial transmission Transfusion Associated Circulatory Overload (TACO)

PlaNeT-2: Serious platelet transfusion related adverse event


F15 – Serious platelet transfusion related adverse event


PlaNeT-2: End of study

Data collection will cease when the baby is 38 weeks corrected gestational age or time of discharge home

Cranial Ultrasound at End of Study (F11)

End of Study (F12)


F11 – Cranial USS at the end of study


F12 – End of study


• Inform the local PlaNeT-2 team if neonate transferred out

of recruiting unit

• Keep all the forms, do not send them with the patient

• If a cranial USS has no been done in the last 7 days,

please perform one before the baby leaves.

PlaNeT-2: Transfer out of recruiting unit


PlaNeT-2: Two years follow up

Thames Regional Perinatal Outcome Group/ Standard Electronic Neonatal Database/ National Neonatal Audit Programme (TRPG/SEND/NNAP) 2- year corrected age outcome form


• Black ink

• For platelet count use the date and time the sample is received in

the lab

• Do not leave blank fields, enter leading zeros

• Any data incorrectly recorded must be crossed through with a single

line and the correct value documented by the side. All corrections

must be initialled and dated by the individual making the changes

PlaNeT-2: Data Quality


• Check what you need to score from the CRFs

• Follow the Unit’s guidelines • Good quality shot of the right view

• Ask for a second opinion to a senior staff if you need

PlaNeT-2 is a trial based on these USS so that all scans are reviewed at

local level and overseen nationally.

PlaNeT-2: Data Quality – Cranial USS


• Local queries:

• For general trial queries: contact Karen Willoughby; copy Ana Mora.

• For medical queries regarding transfusions, SAEs, grading major/severe bleeds or transfusion reactions contact Simon Stanworth, Anna Curley or Vidheya Venkatesh.

PlaNeT-2: Communications

www.planet-2.com


Two criteria to put a baby’s sticker in the PlaNeT-2 book

• Baby born at less than 34 weeks GA

• Platelets <100


What is the right documentation of consent?

• Three copies of the consent forms signed.

Original in site file• Complete documentation of parental

discussion in the notes


(Please add here examples of your current

documentation practice)

Our practice documenting…


If the baby is consented and his platelets go up to 52 then 51 and then 50 in next three days, what

should you do?

I should wait. As long as the platelet count is 50

or above, the baby can not be randomised.


Two places where you can find forms

• In the PlaNeT-2 box behind the desk

• Online at www.planet-2.com


Where are the details to access to www.sealedenvelope.com?

In the PlaNeT-2 book


What is wrong with this data collection plan?


So, is this plan right now?


Is this a better plan then?

Completed: 48%


How can you know at glance what form is due to be completed?

Looking at the front of the pack;

each PlaNeT-2 baby has a

form with the due dates.


CRF Game

• You will be given 4 CRF Forms :

• 5 – Find 3 sets of mistakes

• 6 - Which two corrections are right?

• 7 - Can you find the two missing fields?

• 9 – What is missing?


Find the three sets of mistakes


Which two corrections are

right?


Can you find the two missing fields?


The baby is transferred out of the Unit, three things you should do:

• Inform the PlaNeT-2 team• Keep all the PlaNeT-2 forms• A cranial USS if none has been done in

the last 7 days


Where is the PlaNeT-2 box kept?


What should you do if an enrolled baby develops a rectal bleeding?

Inform the PlaNeT-2 team.

(A rectal bleeding is a major bleed that

should be reported as soon as possible)


What should you do if a SAE happens?

• Proceed as Trust protocol indicates for that

situation• Inform the research team as soon as possible


If you are not sure, what two things you should do?

• Ask us!! We are here to support you.

• Check on-line: www.planet-2.com


Thank you!

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