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Trial registered on ANZCTR


Registration number
ACTRN12612000584831
Ethics application status
Approved
Date submitted
28/05/2012
Date registered
30/05/2012
Date last updated
11/09/2019
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
Gender
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
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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)
Address [1] 285329 0
PO Box 5541, Wellesley Street, Auckland 1141, New Zealand
Country [1] 285329 0
New Zealand
Funding source category [2] 296084 0
Charities/Societies/Foundations
Name [2] 296084 0
Cure Kids
Address [2] 296084 0
PO Box 90 907
Victoria Street West
Auckland 1142
New Zealand
Country [2] 296084 0
New Zealand
Funding source category [3] 298917 0
Charities/Societies/Foundations
Name [3] 298917 0
Auckland Medical Research Foundation
Address [3] 298917 0
Ground Floor, 89 Grafton Road
P O Box 110139, Auckland Hospital
Auckland 1148
Country [3] 298917 0
New Zealand
Funding source category [4] 298918 0
Charities/Societies/Foundations
Name [4] 298918 0
Neurological Foundation NZ
Address [4] 298918 0
66 Grafton Road, Grafton, Auckland?PO Box 110022, Auckland City Hospital, Auckland 1148
Country [4] 298918 0
New Zealand
Funding source category [5] 298919 0
Other Collaborative groups
Name [5] 298919 0
Mercia Barnes Trust RANZCOG
Address [5] 298919 0
PO Box 10611, The Terrace, WELLINGTON 6143
Country [5] 298919 0
New Zealand
Funding source category [6] 298920 0
Charities/Societies/Foundations
Name [6] 298920 0
Maurice & Phyllis Paykel Trust
Address [6] 298920 0
PO Box 110008
Auckland Hospital
Auckland 1148
Country [6] 298920 0
New Zealand
Funding source category [7] 298921 0
University
Name [7] 298921 0
University of Auckland FRDF
Address [7] 298921 0
Private Bag 92019, Auckland 1142, New Zealand
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
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
k.groom@auckland.ac.nz
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
k.groom@auckland.ac.nz
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
k.groom@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 4707 0
Groom KM, McCowan LM, Mackay LK, Lee AC, Gardener G, Unterscheider J, Sekar R, Dickinson JE, Muller P, Reid RA, Watson D, Welsh A, Marlow J, Walker SP, Hyett J, Morris J, Stone PR, Baker PN. STRIDER NZAus: A multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction. BJOG 2019, 126(8):997-1006. doi: 10.1111/1471-0528.15658.
Attachments [1] 4707 0
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary