Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612000584831
Ethics application status
Approved
Date submitted
28/05/2012
Date registered
30/05/2012
Date last updated
19/03/2021
Date data sharing statement initially provided
11/02/2019
Date results information initially provided
11/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
STRIDER (NZAus): A randomised placebo-controlled trial of a new therapy (sildenafil) to help growth in severely growth restricted fetuses at very early gestations.
Scientific title
STRIDER (NZAus): A randomised placebo controlled trial of sildenafil therapy to improve fetal growth velocity in dismal prognosis early-onset intrauterine growth restriction (New Zealand and Australia).
Secondary ID [1] 280564 0
Nil
Universal Trial Number (UTN)
U1111-1131-2408
Trial acronym
STRIDER (NZAus)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe early onset fetal growth restriction 286567 0
Condition category
Condition code
Reproductive Health and Childbirth 286840 286840 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sildenafil 25mg three times a day as an oral tablet from randomisation until delivery (or 32 weeks gestation, whichever occurs first).
Intervention code [1] 284948 0
Treatment: Drugs
Comparator / control treatment
Placebo. Identical in appearance to sildenafil (film-coated, rounded-diamond-shaped tablets).
Control group
Placebo

Outcomes
Primary outcome [1] 287196 0
The proportion of pregnancies with increased abdominal circumference (AC) growth velocity post treatment compared to pretreatment.
Timepoint [1] 287196 0
Post-treatment growth velocity will be calculated 14 days after treatment commenced (if delivered prior then at 10, 5 or 2 days post-treatment).
Secondary outcome [1] 297603 0
Mean absolute change in abdominal circumference (mm) per day
Timepoint [1] 297603 0
14 days after treatment commenced (if delivered prior then at 10, 5 or 2 days post-treatment).
Secondary outcome [2] 297604 0
Mean birthweight and mean birthweight centile
Timepoint [2] 297604 0
At time of delivery
Secondary outcome [3] 297605 0
Changes in uteroplacental, umbilical and fetal Doppler waveform studies.
Timepoint [3] 297605 0
2, 5, 10 and 14 days after treatment commenced.
Secondary outcome [4] 297606 0
Randomisation-to-delivery interval
Timepoint [4] 297606 0
At time of delivery
Secondary outcome [5] 297607 0
Measures of neonatal outcome; live-births, survival to hospital discharge, major morbidity including chronic lung disease requiring ambulatory oxygen therapy on hospital discharge, intraventricular haemorrhage grade 3-4, >grade 2 retinopathy of prematurity, necrotising enterocolitis, number of doses of surfactant, ventilator days, supplemental oxygen days and number of days to full feeds
Timepoint [5] 297607 0
to time of hospital discharge
Secondary outcome [6] 344154 0
Primary outcome of the childhood follow up assessment (STRIDER NZAus Childhood Follow Up Study): Survival free of neurosensory impairment at 2.5 years’ corrected age, defined by absence of cerebral palsy, deafness, blindness, cognitive delay (Bayley-III composite score cognition or language >1 SD below test mean) and motor delay (Bayley-III composite motor score >1 SD below test mean).
Timepoint [6] 344154 0
2.5 years' corrected age (+/- 6 months)

Eligibility
Key inclusion criteria
1. Singleton pregnancy.
2a. At 22+0 weeks to 27+6 weeks: AC measure less than or equal to 3 percentile for gestational age; OR
2b. At 28+0 weeks to 29+6 weeks ultrasound estimate of fetal weight (EFW) <700grams.
Minimum age
No limit
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known major fetal anomaly/syndrome/congenital infection deemed to be the likely cause of IUGR.
2. Known fetal aneuploidy.
3. Already made plan for termination of pregnancy.
4. Maternal disease (e.g. pre-eclampsia) where it is expected that delivery is necessary within 48 hours.
5. Any contraindication to sildenafil therapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will be by central randomisation by phone/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomised stratified for gestational age at recruitment (less than 24 weeks vs. greater than or equal to 24 weeks) and present or absent/reversed end diastolic flow in umbilical arteries.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2014
Actual
11/03/2014
Date of last participant enrolment
Anticipated
Actual
17/03/2017
Date of last data collection
Anticipated
31/12/2019
Actual
28/02/2020
Sample size
Target
122
Accrual to date
Final
122
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment outside Australia
Country [1] 4336 0
New Zealand
State/province [1] 4336 0

Funding & Sponsors
Funding source category [1] 285329 0
Government body
Name [1] 285329 0
Health Research Council of NZ (HRC)
Country [1] 285329 0
New Zealand
Funding source category [2] 296084 0
Charities/Societies/Foundations
Name [2] 296084 0
Cure Kids
Country [2] 296084 0
New Zealand
Funding source category [3] 298917 0
Charities/Societies/Foundations
Name [3] 298917 0
Auckland Medical Research Foundation
Country [3] 298917 0
New Zealand
Funding source category [4] 298918 0
Charities/Societies/Foundations
Name [4] 298918 0
Neurological Foundation NZ
Country [4] 298918 0
New Zealand
Funding source category [5] 298919 0
Other Collaborative groups
Name [5] 298919 0
Mercia Barnes Trust RANZCOG
Country [5] 298919 0
New Zealand
Funding source category [6] 298920 0
Charities/Societies/Foundations
Name [6] 298920 0
Maurice & Phyllis Paykel Trust
Country [6] 298920 0
New Zealand
Funding source category [7] 298921 0
University
Name [7] 298921 0
University of Auckland FRDF
Country [7] 298921 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Park Road, Grafton, Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 284183 0
Hospital
Name [1] 284183 0
Auckland City Hospital
Address [1] 284183 0
Park Road
Grafton
Auckland 1023
Country [1] 284183 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287344 0
Northern A Health and Disability Ethics Committee, New Zealand
Ethics committee address [1] 287344 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
New Zealand
Ethics committee country [1] 287344 0
New Zealand
Date submitted for ethics approval [1] 287344 0
28/05/2012
Approval date [1] 287344 0
02/10/2012
Ethics approval number [1] 287344 0

Summary
Brief summary
Intrauterine growth restriction (IUGR) describes conditions where fetuses are smaller than expected for their gestational age. This puts the fetus at risk of death, hypoxia and preterm birth. If IUGR occurs early in pregnancy (i.e before 28 weeks gestation) survival rates are only 70% and survival free of major handicap (intact survival) is much lower at 20%. Current management involves intensive fetal surveillance and delivery when there is evidence of serious compromise (to avoid death in utero) but this leads to the consequent risks of prematurity. There is no known treatment for IUGR.
This is a double blind randomised placebo controlled trial of Sildenafil, a nitric oxide donor drug, that has the potential to vasodilate uteroplacental vessels improving placental function. It may represent a novel therapy for IUGR. It has been used in pregnancy without adverse events and in a small case-control study it improved daily fetal growth velocity. Women with severe early onset IUGR will be invited to take part in the study at MFM units across NZ and Australia. This study will demonstrate if Sildenafil improves fetal growth, the results will be used in collaboration with other similar studies planned worldwide to demonstrate if Sildenafil improves rates of survival free of major handicap.
This trial incorporates the STRIDER NZAus Childhood Outcome Study: a follow up assessment of all surviving children at 2-3 years’ corrected age to determine whether any benefit (or harm) seen in the newborn as a consequence of antenatal sildenafil therapy is sustained, or develops, through childhood.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34231 0
Dr Katie Groom
Address 34231 0
Department of Obstetrics and Gynaecology, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019 Auckland 1142, New Zealand
Country 34231 0
New Zealand
Phone 34231 0
+64 9 373 7599 ext 89823
Fax 34231 0
Email 34231 0
[email protected]
Contact person for public queries
Name 17478 0
Dr Dr Katie Groom
Address 17478 0
Department of Obstetrics and Gynaecology
Faculty of Medical and Health Science
University of Auckland
Private Bag 92019
Auckland 1142
Country 17478 0
New Zealand
Phone 17478 0
+64 9 373 7599 ext 89823
Fax 17478 0
Email 17478 0
[email protected]
Contact person for scientific queries
Name 8406 0
Dr Dr Katie Groom
Address 8406 0
Department of Obstetrics and Gynaecology
Faculty of Medical and Health Science
University of Auckland
Private Bag 92019
Auckland 1142
Country 8406 0
New Zealand
Phone 8406 0
+64 9 373 7599 ext 89823
Fax 8406 0
Email 8406 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data underlying published results will be made available to the IPD group and upon request to other researchers.
The STRIDER NZAus trial and the Childhood Outcome Study are part of an international STRIDER IPD Consortium which will include data from four national trials undertaken in NZAus, UK, Netherlands and Canada which will be used in individual patient data (IPD) meta-analyses. It is expected that this collaboration will have sufficient power to assess the effect of sildenafil on survival free of major morbidity to primary discharge from hospital and will also explore effects in early childhood (age 2-3 years).
When will data be available (start and end dates)?
Data will be available from completion of primary analysis for STRIDER NZAus and the STRIDER NZAus Childhood Outcome sub-study. No end date.
Available to whom?
The de-identified data that support the findings of this study will be made available to the IPD Consortium, and upon request to researchers who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee identified for this purpose. Access is subject to approval by the Trial Steering Committee and any ethics requirements.
Available for what types of analyses?
Any purpose approved by the Trial Steering Committee.
How or where can data be obtained?
By contacting the Principal Investigator via email: [email protected]. Access subject to approvals by Trial Steering Committee.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11092Study protocolGroom, K., Baker, P., McCowan, L., Stone, P., & Lee, A. (2016, May 18). STRIDER (NZAus): A Randomised Controlled Trial of Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction (New Zealand and Australia). Zenodo. http://doi.org/10.5281/zenodo.56150  
11093Statistical analysis planGroom, Katie, Mackay, Laura, & Lee, Arier. (2017, August 15). STRIDER (NZAus): A Randomised Controlled Trial of Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction (New Zealand and Australia) - Statistical Analysis Plan. Zenodo. http://doi.org/10.5281/zenodo.998139  



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Groom KM, McCowan LM, Mackay LK, Lee AC, Gardener ... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSTRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.2019https://dx.doi.org/10.1111/1471-0528.15658
N.B. These documents automatically identified may not have been verified by the study sponsor.