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Edition 35 August 2019
Kia ora. In this edition of the OTN newsletter we highlight the PROTECT trial currently recruiting in Christchurch and Wellington, we
look at antimicrobial-impregnated central venous catheters in neonates in update your practice, present ‘The Hub’ as a highly
valuable clinical trials resource, and celebrate the OBLIGE trial with cake. We hope you enjoy this month’s OTN news.
ON TRACK News
Trial Development Workshop
2020 Do you have an idea for a clinical
trial? The OTN Trial Development Work-
shop is now being planned for 2020 and
we will be calling for applications in Sep-
tember. These 2 day workshops provide a
fantastic opportunity to develop trial con-
cepts into trial protocols and action plans
for high quality funding applications.
Previous workshops have been very suc-
cessful with several concepts now active
clinical trials. We have received great
feedback from previous workshops and
really encourage anyone with a burning
research question to take up this valuable
opportunity or to just come along to see
how it works.
“Such a positive, supportive environment”
“I liked the involvement of consumers; a non-
threatening audience and setting was created”
“A high standard of expertise”
“There was such collegiality with good
discussions”
Featured trial - PROTECT
Intravenous pentoxifylline as
adjunct therapy to improve long-
term disability in preterm infants
The PROTECT trial is an international multicentre trial being led by the UWA,
Perth, Australia. Wellington and Christchurch are currently recruiting in New
Zealand.
Bacterial late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) are major
causes of systemic inflammation in preterm infants. Treatment of LOS and
NEC in preterm infants is limited to antibiotics, supportive care and sometimes
surgery. None of these treatments help to reduce the associated systemic
inflammation, which itself contributes to brain injury and long term disability
for premature infants.
Pentoxifylline is a non-steroidal drug with the potential of suppressing
systemic inflammation induced by LOS or NEC. A recent Cochrane Review sug-
gests that pentoxifylline given with antibiotics in neonatal sepsis, reduces mor-
tality and length of hospital stay. The PROTECT trial will determine if pentoxi-
fylline plus standard treatment in babies born less than 29 weeks gestation
with sepsis or NEC improves survival without disability. The trial will recruit
1800 preterm infants who meet the following criteria:
Gestation < 29 weeks at birth & no anomalies
6-12 hours from blood culture taken and where antibiotics are com-
mencing for suspected late-onset sepsis (>72 hrs from birth) or NEC
The trial primary outcome is survival without disability at 18-24 months of age.
Tobias Strunk has recently visited from Perth and is hoping to get more sites
on board. If your site might be interested contact: [email protected]
For New Zealand site enquiries contact:
PROTECT Trial Coordinator, Wellington: [email protected]
PROTECT Trial Coordinator, Christchurch: [email protected]
http://ontrack.perinatal.org.nz/
@ONTRACKNetwork1
2019 OTN Trial Development Workshop participants
OTN Site Visits Educational site visits have now been scheduled for Whakatane, Auckland City Hospital, Tauranga,
Taranaki and Dunedin. The visits provide a great opportunity for shared learning on best practice informed by clinical trials
evidence in perinatal and maternal health. If you don’t want to miss out on your site’s opportunity to participate feel free to
email [email protected] to find out if your site is currently planning a visit with the Network.
Edition 35 August 2019
Background: Bloodstream infection is associated with high mortality and serious morbidity in preterm babies. Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheter related bloodstream in-fection in adults and children receiving intensive care, but there is a paucity of similar evidence for babies receiving neonatal intensive care.
Methods: This open-label RCT was undertaken in 18 NICUs in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1) to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated) PICC. Random allocation was done with a web-based program, which was centrally con-trolled to ensure allocation concealment. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were determined following an analysis plan that was specified before individuals saw the unblinded data. The primary outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid (CSF) infection between 24h after randomisation and 48h after PICC removal or death. Data was analysed according to the inten-tion-to-treat principle.
Results: Between August 2015 and January 2017, 861 babies (754 [88%] born before 32 weeks of gestation) were randomly assigned to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median time to PICC removal was 8.20 days (IQR 4·77–12·13) in the antimicrobial-impregnated PICC group versus 7.86 days (5·00–12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89–1·18, p=0·73), with 46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologi-cally confirmed bloodstream or CSF infection. The time from random allocation to first bloodstream or CSF infection was similar between the two groups (HR 1·11, 95% CI 0·73–1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal were similar between the two groups, although rifampicin resistance in posi-tive cultures of PICC tips was higher in the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16–10·57, p=0·018). 60 adverse events were reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies in the standard PICC group.
Authors conclusions: The authors found no evidence of benefit or harm associated with miconazole and rifampicin -impregnated PICCs compared with standard PICCs for newborn babies. They concluded, future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection.
What do these results mean for practice: These results mean antimicrobial-impregnated CVCs offer no benefit and so should not be used. The PREVAIL trial is the largest trial to date of this intervention for this population. The trial is of high methodo-logical quality and power due to its coordinated approach with 18 units involved. Although no evidence of benefit was found, the trial has addressed the need for a large RCT. The results of this trial are important as they contradict findings for the same intervention in older children and adults, supporting standardised evidence based care and informing future research for anti-microbial-impregnated CVC specifically in neonates.
http://ontrack.perinatal.org.nz/
@ONTRACKNetwork1
New Trial Early Colonisation with Bacteria After Birth
There is growing evidence linking caesarean section (CS) to an increased risk of offspring developing obesity and immune disorders such as asthma and diabetes and that this may be due to an altered gut microbiome. Contact with maternal vaginal microbes during vaginal birth is a source of the baby’s developing gut microbiome. Babies born by CS birth are not exposed to vaginal microbes. It has been suggested, but is not yet known, that ‘vaginal seeding’ (mimicking the normal contact with vaginal microbes) may counteract this.
The ECOBABe study is the first RCT to explore this question. The trial has been designed to evaluate the efficacy of oral admin-istration of maternal vaginal bacteria to babies born by caesarean section (CS), or ‘vaginal seeding’, for the establishment of a healthy gut microbiome.
The trial will recruit 80 women having elective CS and 40 women planning vaginal births (reference group) across three New Zea-land hospitals. Half the babies from the CS group will receive the vaginal seeding, and the other half will receive placebo. Infants will be followed up for 3 months. The RCT is currently recruiting at Auckland City, Counties Manukau and Waitemata Hospitals.
For further information you can visit the trial web page https://www.auckland.ac.nz/en/liggins/in-the-community/clinical-studies/clinical-studies-pregnancy/ecobabe-study.html Or, email: [email protected]
Update your practice - Antimicrobial-impregnated central venous
catheters for prevention of neonatal bloodstream infection. The
PREVAIL Trial http://dx.doi.org/10.1016/S2352-4642(19)30114-2
Edition 35 August 2019
Celebrating an OBLIGE milestone with cake
The team at Tauranga hospital recruited the 500th OBLIGE trial participant, and the trial’s
Principal Investigator thought that deserved a celebration—quite right!
To acknowledge the team’s efforts and thank them for their fabulous contribution
to the OBLIGE trial, the team at Tauranga Maternity Unit were pleasantly sur-
prised with a celebratory cake for recruiting the 500th woman into the trial. We
have it on good authority that the cake was delicious!
The OBLIGE trial is currently recruiting women across 11 New Zealand sites: Auck-
land, Dunedin, Hawke's Bay, Hutt Valley, North Shore, Taranaki, Tauranga,
Waikato, Waitakere, Wellington, and Whakatāne.
The objective of the OBLIGE trial is to demonstrate clinical effectiveness, safety
and cost effectiveness for mothers and babies who are allowed to go home after
commencing induction of labour (IOL) with balloon, versus remaining in hospital
after commencing IOL with prostaglandin gel.
The trial is approximately a third of the way towards meeting its recruitment
target of 1552 women. If your site might be interested in coming on board, you
can find out more abut the trial on the OBLIGE trial website:
www.oblige.auckland.ac.nz
http://ontrack.perinatal.org.nz/
@ONTRACKNetwork1
The CCRH also known as ’the Hub’ provides support across all aspects of clinical trial management. The Hub’s aims are to:
Support best practice in clinical trials research
Develop essential infrastructure and resources to conduct high-quality maternal and perinatal clinical trials
Provide cost-effective randomisation and data management solutions
Streamline the process of setting up and running clinical trials
Build on maternal and perinatal research capacity throughout New Zealand
Resources provided:
Check out the CCRH’s Wiki page, which contains a wealth of information and resources for the development and delivery of clinical trials: https://wiki.auckland.ac.nz/researchhub. The resources available include guides, consensus statements, checklists, training and other useful links—all for free.
Services on offer:
Expertise is provided for data system design and trial set up and management, including development of custom web dashboards for day to day trial activities and data safety monitoring purposes. The CCRH is also skilled in supporting long-term follow-up of trial participants.
The CCRH specialises in integrated screening, randomisation and trial databases, and supports fully electronic CRFs. The team are very proud to be successfully supporting several large paperless trials.
Although having a track record of delivering trials largely in obstetrics and neonatology, the CCRH is now providing sup-port for clinical trials in other disciplines too.
The core CCRH team consists of trialists, research nurses, developers, database managers, statisticians and research assistants representing broad clinical trials experience. They are always happy to meet with researchers in the early trial design and planning phase to work with them to develop data manage-ment systems suited to their specific needs.
Work is undertaken on a competitive cost-recovery basis, and if you would like to find out more the team would be happy to meet with you to discuss your clinical trial and to provide a quote for the purpose of grant submissions.
To discuss the services that the CCRH is able to offer you, please contact: [email protected]
Pictured: Tauranga Midwives Paula Chadwick
(left) and Paula Gaffney
About ‘The HUB’ Maternal and Perinatal Central Coordinating Research Hub (CCRH)
Congratulations too to Dunedin for recruiting their first
OBLIGE participant –well done team!
Edition 35 August 2019
Spotlight on Guidelines - Pulse Oximetry Screening
Pulse Oximetry Screening (POS) uses a small Band-Aid-like wrap placed around a baby's foot, with a
light sensor inside that measures oxygen saturation of the blood. It is a simple, non-invasive test that
can be completed in a matter of minutes to detect critical congenital heart defects, the most com-
mon birth defect in newborn babies. Recently the UK National Screening Committee (NSC) an-
nounced it is not recommending routine POS in the UK on the grounds of insufficient evidence of
overall improvement in newborn outcomes, concerns about parental anxiety following a positive test, and that delayed dis-
charge and unnecessary investigations and treatment may outweigh benefits. There is currently a consultation underway in
the UK regarding this decision, which has caused concern amongst the UK clinical community. An interesting commentary was
published online in The Lancet in July, which we encourage those interested to take a look at (https://doi.org/10.1016/S0140-
6736(19)31515-6).
What’s happening in NZ, and how may POS perform here? A pulse oximetry screening feasibility study has been conducted
(April 2016 to April 2018) in Auckland, Lakes and Counties DHBs. The study included hospitals and primary birthing units.
Those involved in this New Zealand research are currently formulating a report and recommendations for the National Screen-
ing Advisory Committee. New Zealand researchers hope that screening can be offered to all newborn babies across the
country, but they acknowledge there are some challenges ahead. Papers will be published shortly.
Recruiting Trials
Currently Recruiting New Zealand
recruits
C*STEROID feasibility
C*STEROID Feasibility: Corticosteroids before planned CS form 35+0 to 39+6 weeks 8
DIAMOND DIfferent Approaches to MOderate & late preterm Nutrition 237
GEMS Gestational Diabetes Mellitus Trial of Diagnostic Detection Thresholds 3788
LATTE Dosage
The most effective and best tolerated dose of caffeine to reduce intermittent hypoxaemia 35
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
543
PAEAN Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy with Erythropoietin
49
PIPPA Paracetamol and Ibuprofen in Primary Prevention of Asthma 976
PLUSS Preventing Chronic Lung Disease in Extremely Preterm Infants Using Surfactant + Steroid 25
PROTECT IV pentoxifylline as adjunct therapy to improve long-term disability in preterm infants 16
Recruitment completed with follow up to primary outcome
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
TARGET follow up study Optimal glycaemic targets for women with gestational diabetes: the randomised trial
http://ontrack.perinatal.org.nz/
@ONTRACKNetwork1
Joan Donley Midwifery Research Forum Palmerston North 12-13th Sept 2019 https://www.midwife.org.nz/midwives/research/joan-donley-midwifery-research-collaboration-jdmrc/jdmrc-forum/
ACTA International Clinical Trials Conference Sydney 2-5th Oct 2019 http://www.clinicaltrialsalliance.org.au/events-forums/acta-international-clinical-trials-conference-2019/
PSNZ Annual ASM Wellington 4-6th Nov 2019 https://perinatalsociety.org.nz/
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/
