INIS Collaborators’s INIS Collaborators’s Meeting PSANZ Meeting PSANZ

4 April 20064 April 2006

Total        117 centresTotal        117 centresTotal     2272 babiesTotal     2272 babies

Well done, thank you for your hard work!Well done, thank you for your hard work!

Because the event rate is higher than originally Because the event rate is higher than originally planned, the UK MRC have revised the target planned, the UK MRC have revised the target sample size from 5,000 to 4,000 to preserve sample size from 5,000 to 4,000 to preserve power to show a 14% Relative Risk Reduction. power to show a 14% Relative Risk Reduction.

MRC have also awarded an extra year’s fundingMRC have also awarded an extra year’s funding

INIS TRIAL UPDATE INIS TRIAL UPDATE MEETING AGENDAMEETING AGENDA

Websites [google: inis ctc] Websites [google: inis ctc] Current recruitment and follow upCurrent recruitment and follow up MRC funding extension till June 2007MRC funding extension till June 2007 Revised sample size Revised sample size ~ 4,000 ~ 4,000 Recommencement of European/ Argentinean sitesRecommencement of European/ Argentinean sites Neonatal sepsis, inflammation and anti-Neonatal sepsis, inflammation and anti-

inflammatory therapiesinflammatory therapies Video consent study Video consent study

Any Other BusinessAny Other Business

inis websiteinis website

[Google] [Google]

inis ctcinis ctc

Australian recruitment 2006Australian recruitment 2006   Grand total Jan Feb Mar

Canberra 88 1 1  

RPA Women and Babies 31   2  

Royal North Shore 43     2

Westmead 118 2 1  

John Hunter, Newcastle 99 3 1 2

Liverpool 34 1   2

Royal Hospital for Women 61 2 1 3

Nepean 23 3    

Children's Hospital at Westmead 4      

Monash Medical Centre 86 3    

Royal Women's, Melbourne 21 3 1 2

Mercy Hospital for Women 104 2 2  

Royal Children's, Melbourne 42   4  

Royal Women's, Brisbane 15      

Flinders Medical Centre 6      

Women's and Children's 9     1

Royal Hobart 26   2  

Totals 810 20 15 12

New Zealand New Zealand recruitment 2006recruitment 2006

   Grand total Jan Feb Mar

National Women's 65 5 7 3

Christchurch Women's 90 5 3 4

Dunedin 19 5 1  

Middlemore 23      

Palmerston North 14 2   1

Waikato 22     3

Wellington Women's 23 1 2 2

Totals 256 18 13 13

TOTAL RECRUITMENT ANZTOTAL RECRUITMENT ANZ

= 1071 in 24 centres= 1071 in 24 centres

Total centres and Total centres and babies worldwidebabies worldwide

ANZ             24 ANZ             24 Total babies 1071Total babies 1071

UK               64 UK               64 Total babies 1120Total babies 1120

Denmark       3Denmark       3Belgium         1Belgium         1Eire               2Eire               2Serbia           1 Serbia           1 Greece           1Greece           1Argentina     21 Argentina     21 Total babies 81Total babies 81

Total centres: 117 Total centres: 117 Total babies: 2272Total babies: 2272

Recruitment was temporarily suspended in Recruitment was temporarily suspended in UK, Europe and Argentina in Jan 2006UK, Europe and Argentina in Jan 2006

Until compliance with new documentation Until compliance with new documentation requirements for good manufacturing requirements for good manufacturing practicepractice

Not because of any safety issue with the Not because of any safety issue with the Scottish IVIG productScottish IVIG product

Recruitment recommenced 24 March in Recruitment recommenced 24 March in UK, Europe and ArgentinaUK, Europe and Argentina

Argentina have 21 centresArgentina have 21 centres Estimated contribution of 50 babies per monthEstimated contribution of 50 babies per month

1 year follow up1 year follow up

Important to maintain contact with families at 1 year to Important to maintain contact with families at 1 year to maximize the 2 year follow up ratemaximize the 2 year follow up rate

490 babies have reached 1 year corrected for gestation490 babies have reached 1 year corrected for gestation

452 babies have complete data452 babies have complete data

37 have data pending37 have data pending 1 is presumed lost to follow up1 is presumed lost to follow up

2 year Follow up2 year Follow up ANZ sitesANZ sites

205 babies surviving babies have reached 2 205 babies surviving babies have reached 2 years corrected for gestationyears corrected for gestation

Currently 180 (88%) have complete dataCurrently 180 (88%) have complete data

24 have appointments pending24 have appointments pending 1 is lost (? Moved to Samoa)1 is lost (? Moved to Samoa)

Expected rate of 2 year follow up is 99%Expected rate of 2 year follow up is 99%

MRC extension funding MRC extension funding applicationapplication

UK MRC has funded an extra year’s UK MRC has funded an extra year’s funding for UK/ European and Australian funding for UK/ European and Australian sites.sites.

This will extend recruitment in Australia This will extend recruitment in Australia until mid or late 2007until mid or late 2007

Revised sample sizeRevised sample size

% primary % primary outcomeoutcomein control in control groupgroup

% primary % primary outcomeoutcomein treatment in treatment groupgroup

Relative riskRelative riskreduction (%)reduction (%)

Total sample Total sample sizesize

3030 25.825.8 1414 4,8844,884

3434 29.229.2 1414 4,0904,090

36.536.5 31.531.5 1414 3,8483,848

Neonatal sepsis, inflammation Neonatal sepsis, inflammation and anti-inflammatory therapiesand anti-inflammatory therapies

Neonatal inflammation is an important Neonatal inflammation is an important determinant of white matter damagedeterminant of white matter damage

IVIG has multiple immuno-modulatory IVIG has multiple immuno-modulatory propertiesproperties

IVIG is an important candidate as an anti-IVIG is an important candidate as an anti-inflammatory therapy in neonatal sepsisinflammatory therapy in neonatal sepsis

Reviews of the evidence that Reviews of the evidence that perinatal inflammation predisposes perinatal inflammation predisposes

to neonatal brain damageto neonatal brain damage

Inflammation and preterm birthInflammation and preterm birth John NewnhamJohn Newnham

Inflammation and the developing human brainInflammation and the developing human brain Don PeeblesDon Peebles

Antenatal inflammation: consequences for Antenatal inflammation: consequences for neonatal immunologyneonatal immunology Alan JobeAlan Jobe

Can a 500 g baby Can a 500 g baby mount an “over-mount an “over-inflammatory” inflammatory” response?response?

INIS is addressing a major research INIS is addressing a major research questionquestion

Does IVIG reduce mortality and morbidity Does IVIG reduce mortality and morbidity in infants with suspected or proven in infants with suspected or proven neonatal infection?neonatal infection?

A CONSENT DVD DESIGNED TO IMPROVE A CONSENT DVD DESIGNED TO IMPROVE CONSENT UPTAKE TO RANDOMISED CONSENT UPTAKE TO RANDOMISED

CONTROLLED TRIALS IN NEONATOLOGY:CONTROLLED TRIALS IN NEONATOLOGY:

A PILOT STUDY IN THE INIS NETWORKA PILOT STUDY IN THE INIS NETWORK

Priya Duggal-Beri, Phyllis Butow, Wendy Priya Duggal-Beri, Phyllis Butow, Wendy Hague , Val Gebski, Lorraine O’Regan, Hague , Val Gebski, Lorraine O’Regan, William Tarnow-Mordi; on behalf of the William Tarnow-Mordi; on behalf of the

International Neonatal Immunotherapy International Neonatal Immunotherapy Study (INIS) Collaborative Group.Study (INIS) Collaborative Group.

Barriers to participation in Barriers to participation in randomised controlled trials: randomised controlled trials:

a systematic review.a systematic review.Ross et al 1999Ross et al 1999

Clinician barriers included:Clinician barriers included: • time constraints time constraints • lack of staff and traininglack of staff and training • worry about the impact on the doctor-worry about the impact on the doctor-

patient relationship patient relationship • concern for patients concern for patients • loss of professional autonomy loss of professional autonomy • difficulty with the consent proceduredifficulty with the consent procedure • lack of rewards and recognition lack of rewards and recognition • insufficiently interesting question.insufficiently interesting question.

Patient barriers included:Patient barriers included:

• additional demands of the trialadditional demands of the trial

• patient preferencespatient preferences

• worry caused by uncertaintyworry caused by uncertainty

• concerns about information and consent.concerns about information and consent.

There is no evidence on the impact of Digital There is no evidence on the impact of Digital Video Decoders (DVDs) or videos on Video Decoders (DVDs) or videos on knowledge knowledge or confidence of staff in obtaining consent, and or confidence of staff in obtaining consent, and on uptake of consent by parents. on uptake of consent by parents.

We explored the effectiveness of a DVD/ video We explored the effectiveness of a DVD/ video and accompanying booklet in 24 INIS sites inand accompanying booklet in 24 INIS sites in describing consent delivery methods describing consent delivery methods improving knowledge about the INIS trial. improving knowledge about the INIS trial.

VINIS: Video/ DVD + Booklet VINIS: Video/ DVD + Booklet site intervention studysite intervention study

A pilot RCT in 24 ANZ INIS sites to A pilot RCT in 24 ANZ INIS sites to explore explore whether a video and booklet for staff who whether a video and booklet for staff who

seek consent can improve their knowledge seek consent can improve their knowledge and confidence and confidence

its potential effect on recruitment rate.its potential effect on recruitment rate.

1645 Wednesday 51645 Wednesday 5thth April April Level 2 Meeting Room 11Level 2 Meeting Room 11

Data Collection issuesData Collection issues

Excellent rate of completion and accuracy of Excellent rate of completion and accuracy of CRFsCRFs

Consent formsConsent forms Please ensure that all signatures by parents and Please ensure that all signatures by parents and

investigators and witnesses are completeinvestigators and witnesses are complete HIC consent formsHIC consent forms

Please remember to ask new and old parents to Please remember to ask new and old parents to complete this consent form (for economic analysis)complete this consent form (for economic analysis)

Days of respiratory support after INIS Days of respiratory support after INIS interventionintervention Please include all days the baby received any Please include all days the baby received any

respiratory support in your hospitalrespiratory support in your hospital