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Trial registered on ANZCTR


Registration number
ACTRN12621000354886
Ethics application status
Approved
Date submitted
27/01/2021
Date registered
29/03/2021
Date last updated
27/08/2024
Date data sharing statement initially provided
29/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Reducing operative birth for fetal distress in women with small or suboptimally grown infants - The RidStress 2 Randomised Controlled Trial
Scientific title
Reducing operative birth for fetal distress in women with small or suboptimally grown infants - The RidStress 2 Randomised Controlled Trial
Secondary ID [1] 302753 0
Nil known
Universal Trial Number (UTN)
U1111-1261-0324
Trial acronym
RIDSTRESS 2 (ReducIng fetal DiSTRESS in small or suboptimally grown infants)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Operative birth (caesarean or instrumental birth) 319702 0
Birth asphyxia 319703 0
Small for gestational age infants 319704 0
Condition category
Condition code
Reproductive Health and Childbirth 317628 317628 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 317629 317629 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 317630 317630 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intrapartum Sildenafil Citrate 50mg taken orally, 8 hourly to a maximum of 3 doses (150mg) in 24 hours, given on one day only.

Sildenafil Citrate will be given when the participant is admitted to the birthing unit for the commencement of induction of labour (artificial rupture of membranes +/- syntocinon infusion), or for management of spontaneous labour (regular uterine activity and >/= 4cm dilation on cervical assessment).
Intervention code [1] 319038 0
Treatment: Drugs
Intervention code [2] 319817 0
Prevention
Comparator / control treatment
Intrapartum placebo (capsulated, pre-gelatinised maize starch, no active ingredients), taken orally, 8 hourly to a maximum of 3 doses in 24 hours, given on one day only.

Placebo will be given when the participant is admitted to the birthing unit for the commencement of induction of labour (artificial rupture of membranes +/- syntocinon infusion), or for management of spontaneous labour (regular uterine activity and >/= 4cm dilation on cervical assessment).
Control group
Placebo

Outcomes
Primary outcome [1] 325677 0
Emergency caesarean section for fetal distress (defined contemporaneously as an abnormality in fetal heart rate pattern, fetal scalp lactate or pH level). This will be assessed after review of participant's medical record.
Timepoint [1] 325677 0
At delivery of the baby.
Secondary outcome [1] 388739 0
Any operative birth (caesarean section or instrumental vaginal birth) for fetal distress (defined contemporaneously as an abnormality in fetal heart rate pattern, fetal scalp lactate or pH level). This will be assessed after review of participant’s medical record.
Timepoint [1] 388739 0
At delivery of the baby.
Secondary outcome [2] 391024 0
Health economic costs assessed after review of inpatient and outpatient medical records, emergency department records, Medicare data and prescription pharmaceuticals funded through the PBS scheme.
Timepoint [2] 391024 0
2 years post delivery (when child reaches the age of 2 years)
Secondary outcome [3] 392206 0
Childhood neurodevelopmental outcomes as assessed by a paediatric neuropsychologist. This data will be assessed directly as part of the study protocol. It will not be collected from the medical records.
Timepoint [3] 392206 0
2 years post delivery (when child reaches the age of 2 years)

Eligibility
Key inclusion criteria
1. Singleton pregnancy
2. Planning a vaginal birth at term (>37 weeks gestation)
3. Aged >18 years and able to give informed consent
4. Pregnancy complicated by suspected small for gestational age (SGA) infant or late fetal growth restriction (FGR) (see below definitions)

SGA is defined as Estimated Fetal Weight (EFW) or Abdominal Circumference (AC) <10th centile for gestation based on ultrasound assessment.

FGR is defined as EFW or AC <3rd centile or two out of three of the following:
1. EFW or AC <10th centile.
2. AC or EFW crossing centiles by >two quartiles on growth charts.
3. Cerebroplacental ratio (CPR) <5th centile or Umbilical Artery Pulsatility Index (UA PI) >95th centile for gestation.
Minimum age
18 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Two or more previous CS births
2. Previous classical CS
3. Major fetal anomaly in this pregnancy
4. Non-cephalic presentation
5. Severe hepatic or renal impairment
6. Participants who are taking any type of nitrate drug therapy or who utilize short-acting nitrate-containing medications during labour [such as sodium nitroprusside, bosentan, fosamprenavir and ritonavir combination, hepatic enzyme inhibitors CYP3A4 (including itraconazole, ketoconazole, ritonavir, cimetidine, erythromycin, saquinavir, darunavir), or hepatic enzyme substrates (CYP3A4), medications used to treat pulmonary arterial hypertension, and other phosphodiesterase type 5 inhibitors like riociguat], due to the risk of potentially life-threatening hypotension.

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)
Allocation will be concealed. Participants will be centrally randomised by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random order will be generated by permuted block randomisation with randomly selected block sizes.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The incidence of the primary outcome (caesarean section) is estimated at 30% based on Mater Mother’s Hospital data. To detect a 33% reduction in the primary outcome from 30% to 20% for an alpha of 0.05 and power of 80% with 10% dropout in each arm needs 660 women (330 each arm). This will yield >90% power to detect a similar reduction for the secondary outcome of any operative birth for fetal distress.
Analysis will be by intention to treat. Baseline characteristics for women in the two randomised groups will be compared to check for balance across the groups. Primary and secondary outcomes will be compared between the groups using generalised linear models (binary or normal). Intervention effect will be presented as relative risk (RR) or mean difference (MD), as appropriate, with 95% confidence intervals. Two-tailed P value <0.05 will be considered statistically significant. Primary analyses will be unadjusted. Number needed to screen and treat to prevent one adverse primary outcome will be calculated. Where there are differences in baseline characteristics between study groups that might influence outcomes, secondary adjusted analysis of the primary outcome will be conducted with multiple (log-binomial) regression. No adjustment will be made for multiple comparisons but results will be interpreted with due caution for the risk of Type I error. Findings will be reported in accordance with CONSORT and TRIPOD guidelines.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2021
Actual
28/07/2021
Date of last participant enrolment
Anticipated
11/09/2026
Actual
Date of last data collection
Anticipated
11/09/2028
Actual
Sample size
Target
660
Accrual to date
200
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 18132 0
Mater Mother's Hospital - South Brisbane
Recruitment hospital [2] 18133 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [3] 18394 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [4] 23646 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 32829 0
4101 - South Brisbane
Recruitment postcode(s) [2] 32830 0
4029 - Royal Brisbane Hospital
Recruitment postcode(s) [3] 32831 0
4575 - Birtinya
Recruitment postcode(s) [4] 39066 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 307339 0
Charities/Societies/Foundations
Name [1] 307339 0
Royal Brisbane & Women's Hospital Foundation
Country [1] 307339 0
Australia
Funding source category [2] 307555 0
Charities/Societies/Foundations
Name [2] 307555 0
WishList Sunshine Coast Health Foundation
Country [2] 307555 0
Australia
Funding source category [3] 307556 0
Charities/Societies/Foundations
Name [3] 307556 0
Research Foundation, Cerebral Palsy Alliance
Country [3] 307556 0
Australia
Funding source category [4] 307558 0
Charities/Societies/Foundations
Name [4] 307558 0
RANZCOG Women's Health Foundation - Norman Beischer Clinical Research Scholarship
Country [4] 307558 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Mater Misericordiae Ltd
Address
Raymond Terrace
South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 307979 0
None
Name [1] 307979 0
Address [1] 307979 0
Country [1] 307979 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307287 0
Mater Misericordiae Ltd Human Research Ethics Committee (EC00332) (MML HREC)
Ethics committee address [1] 307287 0
Ethics committee country [1] 307287 0
Australia
Date submitted for ethics approval [1] 307287 0
10/08/2020
Approval date [1] 307287 0
11/09/2020
Ethics approval number [1] 307287 0
HREC/MML/67642

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106694 0
Prof Sailesh Kumar
Address 106694 0
Mater Clinical School - University of Queensland
Mater Health Services
1st Floor Whitty Building
South Brisbane
Queensland 4101
Country 106694 0
Australia
Phone 106694 0
+617 3163 8844
Fax 106694 0
Email 106694 0
sailesh.kumar@mater.uq.edu.au
Contact person for public queries
Name 106695 0
Tegan Triggs
Address 106695 0
Mater Research - University of Queensland
Level 3, Aubigny Place
Raymond Terrace
South Brisbane
Queensland 4101
Country 106695 0
Australia
Phone 106695 0
+617 3163 8844
Fax 106695 0
Email 106695 0
tegan.triggs@health.qld.gov.au
Contact person for scientific queries
Name 106696 0
Sailesh Kumar
Address 106696 0
Mater Clinical School - University of Queensland
Mater Health Services
1st Floor Whitty Building
South Brisbane
Queensland 4101
Country 106696 0
Australia
Phone 106696 0
+617 3163 8844
Fax 106696 0
Email 106696 0
sailesh.kumar@mater.uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the de-identified individual participant data collected during the trial will be made available to other researchers
When will data be available (start and end dates)?
All of the de-identified individual participant data collected during the trial will be made available to other researchers beginning 12 months and ending 5 years after article publication. Data will only be made available to researchers who provide research ethics approval and an appropriate research proposal, with ultimate approval provided by the CIA.
Available to whom?
approved researchers, assessed on individual request basis
Available for what types of analyses?
IPD meta-analysis
How or where can data be obtained?
Requests should be directed to Professor Sailesh Kumar (sailesh.kumar@mater.uq.edu.au).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9753Study protocol    Please contact Prof Sailesh Kumar with enquiries r... [More Details]



Results publications and other study-related documents

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