the administration of probiotic to premature babies to prevent … · 2013-10-01 · the...
TRANSCRIPT
The administration of probiotic to premature babies to prevent infection,
severe intestinal complication and death
IntroductionThis study is a randomised double-blind placebo-controlled trial that will investigate the effect of early administration of a single probiotic strain given to an unselected group of babies at high risk of NEC and sepsis.
BackgroundPreterm babies are at increased risk of bacterial infection and of the severe intestinal complication, necrotising enterocolitis (NEC); both may be fatal and are associated with increased hospitalisation and chronic complications. This is largely because premature babies have immature defences against infection and are more likely to become colonised with bacteria in the environment of the Neonatal Intensive Care Unit that may cause disease.We hypothesise that probiotics given soon after birth will multiply in the intestine improving the baby’s general health and reducing the chance of potentially pathogenic organisms becoming established.
EvidenceThere is increasing evidence that giving probiotics to very preterm babies may reduce the incidence of both NEC and death; the effect upon bloodstream infection is unclear. However, the published studies are all small and have excluded many of the babies at highest risk of poor outcomes. They have all used different combinations of probiotic strains with no quality control of the products used and with only limited information about successful colonisation of the baby’s gut. Consequently we cannot be confident either of efficacy or safety in the high risk preterm babies who we most need to protect.
Eligibility for PiPS• Babies born between 23 and 30 weeks gestation inclusive and• less than 48 hours old and• with written informed parental consent
Exclusion from PiPS• A lethal congenital abnormality known at trial entry or• any known gastrointestinal malformation or• no realistic prospect of survival
Primary OutcomesThe primary outcomes are blood stream infection with any organism other than a skin commensal after 72 hours after birth, necrotising enterocolitis Bell Stage 2 or 3, and death.
Study TreatmentThe active intervention is Bifidobacterium breve strain BBG which is produced under GMP. It is provided as a freeze dried powder with corn starch; the placebo is freeze dried corn starch alone. Before administration 1g foil sachets of the intervention are re-suspended in 1/8th strength Neocate (for blinding purposes) and 1ml of the supernatant is given enterally to the baby.The intervention is given once daily starting as soon as possible after randomisation and continuing until 36 post-menstrual age or discharge from hospital if sooner. Colonisation rates in participating babies will be monitored at 2 weeks post-natal and 36 weeks post-menstrual age.
Participating CentresThere are a total of 45 centres participating in the study which are all based in the South East of England. Twenty-four centres have recruited to the trial and a further 21 centres were required to continue the trial procedures for babies who are routinely transferred between hospitals during their time as inpatients.
Recruiting SitesBarnet HospitalBasildon HospitalCroydon University HospitalHomerton University HospitalJohn Radcliffe Hospital King’s College HospitalLewisham HospitalLuton and Dunstable HospitalMedway Maritime HospitalNewham General HospitalNorth Middlesex HospitalQueen’s Hospital, RomfordThe Royal London Hospital
Royal Sussex County HospitalSouthend HospitalSt George’s HospitalSt Peter’s, ChertseySt Thomas’ HospitalTunbridge Wells Hospital at PemburyWatford General HospitalWhipps Cross HospitalWhittington HospitalWilliam Harvey Hospital, AshfordUniversity College Hospital
Continuing Care SitesAddenbrooke’s HospitalBedford hospitalChase Farm HospitalColchester General HospitalDarent Valley HospitalFrimley Park HospitalGreat Ormond Street HospitalHinchingbrooke’s HospitalHorton General HospitalKing George HospitalLister HospitalNorthampton General HospitalPrincess Royal Hospital,
Haywards HeathPrincess Royal University HospitalQE Hospital, WoolwichQE the QM HospitalRoyal Berkshire HospitalRoyal Free HospitalRoyal Surrey County HospitalStoke Mandeville HospitalWest Suffolk HospitalWexham Park HospitalWorthing Hospital
ContactsPiPS Chief Investigator: Professor Kate CosteloeDepartment of Neonatology, Homerton University Hospital, Homerton Row, London. E9 6SRTel: 07787 518879 Email: [email protected]
PiPS Trial Co-ordinator: Dr Paul HealNPEU, University of Oxford, Old Road Campus, Headington, Oxford. OX3 7LFTel: 01865 617924 Email: [email protected]
Recruitment and Study CloseoutThe target sample size is 1,300 (with 650 babies in each arm) which was reached in July 2013 after a 36 month recruitment period.
0
200
400
600
800
1000
1200
1400
Jul10
Aug10
Sep10
Oct10
Nov10
Dec10
Jan11
Feb11
Mar11
Apr11
May11
Jun11
Jul11
Aug11
Sep11
Oct11
Nov11
Dec11
Jan12
Feb12
Mar12
Apr12
May12
Jun12
Jul12
Aug12
Sep12
Oct12
Nov12
Dec12
Jan13
Feb13
Mar13
Apr13
May13
Jun13
Jul13
Month
Number
Mont hly r ec ruit ment 6 9 9 6 4 16 22 27 22 26 32 41 38 39 35 42 56 39 41 43 60 43 50 42 35 48 54 52 47 44 51 48 53 43 41 30 21
Cumulat ive t ot al 6 15 24 30 34 50 72 99 121 147 179 220 258 297 332 374 430 469 510 553 613 656 706 748 783 831 885 937 984 1028 1079 1127 1180 1223 1264 1294 1315
Projec t ed cumulat ive t ot al ( 45 per mont h)
Projec t ed cumulat ive t ot al ( 50 per mont h)
Jul10
Aug10
Sep10
Oct10
Nov10
Dec10
Jan11
Feb11
Mar11
Apr11
May11
Jun11
Jul11
Aug11
Sep11
Oct11
Nov11
Dec11
Jan12
Feb12
Mar12
Apr12
May12
Jun12
Jul12
Aug12
Sep12
Oct12
Nov12
Dec12
Jan13
Feb13
Mar13
Apr13
May13
Jun13
Jul13
All trial interventions will be completed by the end of October 2013. Data collection and cleaning is anticipated to finish by the end of the year with publication of the study’s final results scheduled for April 2014.
2013 2014Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar AprRecruitment Chase, validate and collate data Analysis & writing up
A: End of recruitment, start of site close-out visits
B: End of trial intervention course, start of intervention reconciliation
C: End of intervention reconciliation, end of site close-out visits (all sites closed), database lock (analysis
D:
E: Publication of main results paper, collaborators
public release of results (press releases)
A B C D E
Co-ordination, Sponsorship and Funding This trial is co-ordinated from the National Perinatal Epidemiology Unit Clinical Trials Unit (NPEU-CTU) at the University of Oxford and is sponsored by Queen Mary, University of London. Funding is provided by the Health Technology Assessment (HTA) programme part of the National Institute of Health Research (NIHR).