Edition 38 November 2019

Kia ora. Welcome to this month’s OTN news and our new bi-line Te Awhi Rito. In this edition we provide a reminder of the upcoming 2020 ON TRACK Network Trial Development Workshop - you can register now for free. We catch up with the PIPPA Tamariki trial and take a look at the A*STEROID trial in ‘update your practice’. We also provide updates on the latest trial accruals, clinical trial resources and save the dates.

ON TRACK News REGISTER NOW for the fourth ON TRACK Network Trial Develop-ment Workshop Auckland City Hospital 20th & 21st February 2020

Register for FREE here: https://uoaevents.eventsair.com/on-track-2020/on-track

We have had some great trial ideas come through our annual workshops. Ideas that have gone on to become active research on the clinical shop floor. The 2020 workshop will be no different. There are going to be some great discussions helping exciting trial ideas become meaningful research for better health for mothers and babies.

This workshop is a fantastic opportunity to learn more about the development of quality clinical trials. Register to come along if you have submitted a trial concept, if you are collaborating on a submitted concept, or if you simply want to contribute your experience and learn—we would love to see you there!

Expression of interest - Māori Representation We are seeking representation for Māori on the ON TRACK Network National Executive Committee. We see this role contrib-uting to all work of the committee but with particular focus on helping to improve health outcomes for wāhine Māori, pēpi and their whānau. Email us if you would like to learn more.

ontracknetwork@auckland.ac.nz

ontrack.perinatalsociety.org.nz/

@ONTRACKNetwork1

Forum for Women & Whānau The ON TRACK Network consumer forum is now officially up and running. The Forum for Women & Whānau communi-cates the benefits of clinical trials to the general public by showcasing clinical trials and reporting consumer stories. It also facilitates two-way partnerships between consumers and clinicians/researchers to enhance:

Research priority setting

Implementation of clinical trials across NZ sites

Co-development of trial ideas and design

Trial specific involvement

Implementation of clinical trials findings into everyday clinical practice

The Forum does this by providing an accessible space via Facebook for consumers to interact, comment, engage and contribute to the Network’s activities. Anyone can join the Forum via Facebook. The role of Forum members is to contribute what they can, when they can to clinical trials discussions and activities. Our aim

is to have a diverse and inclusive membership reflective of the backgrounds, experience, ethnicity and geogra-phy of New Zealanders.

Quarterly Forum for Women & Whānau newsletters will be distributed in whānau rooms and clinic waiting areas to encourage people to join us on Facebook. Newsletters also allow those not using social media the opportunity to join specific projects within the Network including invitations to attend annual OTN Trial Devel-opment Workshops, research prioritisation workshops and trial specific groups. If you would like to learn more, search Forum for Women & Whānau on Facebook or email us for a copy of our forum’s newsletter.

Te Awhi Rito Those observant amongst you will have noticed an

addition to our Network’s logo. While establishing the Forum for Women & Whānau, the Forum’s Advisory Committee highlighted the need for a name that reflects our culture. Committee members discussed this with their whanau and suggested ‘Te Awhi Rito’. Te Awhi Rito comes from the flax bush concept com-monly used in maternity and child health as a metaphor for whānau. The hara-keke (flax) plant represents the family with the centre shoot being the child. It is surrounded by the awhi rito (the parents) as protection. The outside leaves rep-resent the grandparents and ancestors.

Te Awhi Rito received such positive feedback the ON TRACK Network National Executive Committee unanimously agreed it should be applied to the whole Network.

Edition 38 November 2019

Featured trial - PIPPA Tamariki Paracetamol and Ibuprofen in Primary Prevention of

Asthma to determine whether paracetamol compared to ibuprofen for treatment of babies with pain or fever in the first year of life increases the risk of asthma at 6 years of age.

Asthma affects thousands of children each year who often go on to have life-long asthma and other allergic conditions. Although there have been many advances in the management of asthma, the number of children with asthma in New Zealand remains very high. Paracetamol and ibuprofen are safe and effective for relieving pain and fever in babies, but previous obser-vational studies suggest that their use may influence the chance of developing asthma. PIPPA Tamariki will find out if rates of asthma at 6 years of age are different in children who take only paracetamol for pain or fever in their first 12 months, compared to children who take only ibuprofen during this time.

Eligible babies are those: Born in the catchment area of Auckland City, Middlemore, and Wellington hospitals Age less than 8 weeks More than 32 weeks gestation at birth Have had no exposure to paracetamol or ibuprofen since birth

The trial is a collaboration between Auckland, Counties Manukau, and Capital & Coast District Health Boards as well as Auck-land, Otago, Massey and Calgary Universities and the Medical Research Institute of New Zealand. Investigators will recruit 3,922 babies in total. Currently 1,171 babies have been recruited. If you would like to help with this study contact the re-search teams directly: Phone (for all sites): 0800 747 728 Wellington Hospital: Email: pippatamarikiwgtn@mrinz.ac.nz Auckland City Hospital: Email: pippatamariki@adhb.govt.nz Middlemore Hospital: Email: pippatamariki@auckland.ac.nz

Update your practice Maternal intramuscular dexamethasone versus betamethasone before preterm birth (ASTEROID): a multicentre randomised controlled trial. The A*STEROID Trial recently published in The Lancet Child & Adolescent Health (https://doi.org/10.1016/S2352-4642(19)30292-5) recruited women from 14 maternity hospitals in

Australia and New Zealand. The trial was funded by the National Health and Medical Research Council of Australia.

Background: Antenatal corticosteroids given to women before preterm birth improve infant survival and health. However, it has been unclear whether dexamethasone or betamethasone leads to better maternal, neonatal and childhood health outcomes. A*STEROID was designed to assess these. The primary outcome was death or neurosensory disability in children at 2 years corrected age. Secondary outcomes were effects on maternal, infant and childhood health at 2 years including body size, blood pressure and behaviour.

Methods: Women were eligible for A*STEROID if they were at risk of preterm birth before 34 weeks gestation, had a singleton or twin pregnancy, and no contraindications to use of antenatal corticosteroids. Women were randomly assigned to receive two intra-muscular injections of either 12mg dexamethasone (dexamethasone sodium phosphate) or 11.4mg betamethasone (Celestone Chronodose) 24 hours apart.

Results: A total of 1346 women with 1509 fetuses were randomised: 679 (50%) women to receive dexamethasone and 667 (50%) women to receive betamethasone. 27 (4%) and 28 (4%) fetuses, infants, or children in the dexamethasone group and betame-thasone group respectively, died before age 2 years. The primary outcome of death or neurosensory disability at age 2 years was: 198/603 (33%) for dexamethasone compared with 192/591 (32%) for betamethasone (adjusted relative risk [adj RR] 0·97, 95% CI 0·83 to 1·13; p=0·66). Few women reported side effects of the trial medication, 18 (3%) of 679 women in the dexamethasone group and 28 of 667 (4%) women in the betamethasone group. The most frequent side-effect was discomfort at the injection site and was less likely in the dexamethasone group than in the betamethasone group (six [1%] women vs 17 [3%] women; p=0·02). No differences were seen between groups for neonatal morbidity, body size, individual components of the primary outcome, childhood health, blood pressure and behaviour. Unexpectedly, children exposed to dexamethasone were less likely to be hypertensive at 2 years corrected age (115/356 [32%] vs. 144/347 [42%]; adj RR, 0·78, 95% CI 0·64 to 0·95; p=0·02). For the women there were no differences in maternal infectious morbidity, use of induction of labour, postpartum haemorrhage or length of postnatal stay, alt-hough fewer women allocated to dexamethasone had a caesarean birth (295/679 [43%] vs. 346/667 [52%]; adj RR 0·84, 95% CI 0·75 to 0·93; p=0·001).

Summary interpretation: Survival without neurosensory disability at age 2 years does not differ between dexamethasone and be-tamethasone treatment. Either corticosteroid can be used prior to preterm birth to improve infant and child health. It should be noted, dexamethasone is 1/35th of the cost of betamethasone.

What do these results mean for clinical practice and future research? The A*STEROID Trial is the first large trial to report on the comparative effects of dexamethasone and betamethasone on infant morbidity and mortality, long-term childhood health, and maternal outcomes. Survival free of neurosensory disability in children at age 2 years after in-utero exposure was similar for dexa-methasone and betamethasone. Findings from the A*STEROID Trial provide reassurance that both dexamethasone and betame-thasone have similar effects on neonatal health and neurodevelopmental outcome into early childhood.

The A*STEROID findings support current guideline recommendations that either drug can be used for women at risk of preterm birth. The unexpected but potentially clinically important differences of reduced risk of caesarean birth and fewer children being hypertensive at two years of age when exposed to dexamethasone compared to betamethasone needs later assessment as to the impact and clinical relevance. Confirmation in different populations is warranted.

Edition 38 November 2019

ON TRACK Network Educational Site Visits ON TRACK Network educational site visits across the country are in full swing. Site visits aim to provide the latest in evidence-based best practice in maternal and neonatal care on topics selected by sites and talk about the value of clinical trials research and getting involved with the ON TRACK Network.

Visits have taken place at Auckland City (featured in our September edition) and more recently Taranaki, Tauranga and Dunedin hospitals. The feedback we have received from all sites has been overwhelmingly positive with all attendees providing feedback they would be keen to attend similar sessions in the future. We are pleased to hear from many of those who have attended the sessions that the content of the talks designed to provide something for everyone, has done just that, making these multidisciplinary sessions not to be missed!

ontracknetwork@auckland.ac.nz

ontrack.perinatalsociety.org.nz/

@ONTRACKNetwork1

“Key message for me….importance of clinical trials for improving health outcomes, reducing harm and

reducing variation in practice”

“Good discussion on role of multicentre, multidisciplinary clinical trials”

Caroline Crowther &

Esther Calje

Esther presenting fun facts about iron

Chris McKinlay, Katie Groom & Chris Thurnell (Tauranga SNL) A happy crowd at Tauranga

Jane Alsweiler

“The concept that every mother and baby is entitled to participate in a clinical trial is a big shift in thinking for me”

“The session was really engaging and prompted discussion”

“The TARGET Trial results were a revelation...”

“I really liked how multidisciplinary the session was”

All our visits include talks on how getting involved with clinical trials research benefits the women and babies we care for, our own institutions and society as a whole. We also showcase initiatives of the Network and the clinical trials it supports.

Topic specific talks have included:

Taranaki Professor Caroline Crowther: Diagnosis and management of gestational diabetes including presentation of the TARGET Trial results

Esther Calje: Identifying best practice for the management of iron deficiency anaemia in pregnancy and postpartum

Tauranga Associate Professor Katie Groom: Antenatal and intrapartum interventions to improve outcomes after preterm birth – what can midwives and obstetricians do?

Dr Chris McKinlay: Optimising care of late preterm infants for long-term health

Dunedin Dr Jane Alsweiler: Providing optimal nutrition for babies born preterm

Dr Michelle Wise: Induction of labour—developing national guidelines and filling the evidence gaps

“Great visit, very apt speakers”

“Great presentations, very interesting”

Where have

we been?

Before the end of the year we will be visiting Whakatane (as we publish this edition) Gisborne and Palmerston North. More ON TRACK Network educational site visits will be planned for 2020. If your site has not yet taken advantage of this great opportunity speak with your Site Network Leader or feel free to contact us directly (ontracknetwork@auckland.ac.nz).

Edition 38 November 2019

Research News ACTA Launch Consumer Involvement & Engagement Toolkit

Keeping with the consumer focus having now launched our Forum for Women & Whānau, we would like to

highlight a new resource from the Australian Clinical Trials Alliance (ACTA). ACTA supports and represents

networks of clinician researchers performing clinical trials in Australia. However more than 50% of the clinical

trials network active in Australia are bi-national ANZ ones and hence ACTA are very supportive of clinical trials

research in New Zealand too. ACTA produce many useful resources that are relevant to us including their Consumer Involve-

ment & Engagement Toolkit developed with a working group of consumers, researchers and research organisations which

has just been launched. The aim of the Toolkit is to improve knowledge and provide useful resources for consumer involve-

ment and engagement at all stages of clinical trials. Presented as an interactive route map—one for researchers and research

organisations, the other for consumers and the community—it is very user-friendly.

https://involvementtoolkit.clinicaltrialsalliance.org.au/

Recruiting Trials

ontracknetwork@auckland.ac.nz

ontrack.perinatalsociety.org.nz/

@ONTRACKNetwork1

Currently Recruiting New Zealand

recruits

C*STEROID

Feasibility C*STEROID Feasibility: Corticosteroids before planned CS form 35+0 to 39+6 weeks 48

DIAMOND DIfferent Approaches to MOderate & late preterm Nutrition 272

ECOBABe The ECOBABe study (Early Colonisation with Bacteria After Birth) 34

GEMS Gestational Diabetes Mellitus Trial of Diagnostic Detection Thresholds 4146

LATTE

Dosage The most effective and best tolerated dose of caffeine to reduce intermittent hypoxaemia 53

OBLIGE Comparing two methods of starting an induction of labour in pregnant women (balloon at home

versus hormone gel in hospital) to assess chance of vaginal birth 629

PAEAN Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy with

Erythropoietin 52

PIPPA Paracetamol and Ibuprofen in Primary Prevention of Asthma 1,171

PLUSS Preventing Chronic Lung Disease in Extremely Preterm Infants Using Surfactant + Steroid 35

PROTECT IV pentoxifylline as adjunct therapy to improve long-term disability in preterm infants 23

Recruitment completed - follow up to primary outcome ongoing

MAGENTA Magnesium Sulphate at 30 to 34 weeks' gestational age: Neuroprotection Trial

PROVIDE Higher IV protein intake for extremely low birthweight babies in the first week after birth on survival free from neu-

rodevelopmental disability at 2 years' corrected age

Childhood outcome studies

hPOD@2YR Follow-up Study Hypoglycaemia Prevention in newborns with Oral Dextrose

STRIDER NZAus Childhood Outcome

Study Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (2-3 years)

TARGET Follow up Study Optimal glycaemic targets for women with gestational diabetes: the randomised trial

Save the date NZ APEC Study Day Nelson 22nd Nov 2019 http://www.nzapec.com/conference

Paediatric Society of New Zealand 71st ASM Auckland 19th-22nd Nov 2019 https://www.paediatrics.org.nz/events/ Society for Maternal Fetal Medicine 40th Annual meeting Texas 3rd-8th February 2020 https://www.smfm.org/2020 ON TRACK Network Trial Development Workshop 2020 Auckland 20th-21st Feb 2020 on-track.perinatal.org.nz/ PSANZ Annual Congress Sydney 5th-8th April 2020 https://web.cvent.com/event/71fe9307-c088-46ee-99ed-cc19660a089d/summary