COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

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
ACTRN12619001475134
Ethics application status
Approved
Date submitted
23/09/2019
Date registered
24/10/2019
Date last updated
14/02/2020
Date data sharing statement initially provided
24/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
PRECeDe Pilot: Prevention of neonatal Respiratory distress with antenatal corticosteroids prior to Elective Caesarean section in women with Diabetes - A Feasibility Randomised Trial
Scientific title
PRECeDe Pilot: Prevention of neonatal Respiratory distress with antenatal corticosteroids prior to Elective Caesarean section in women with Diabetes - A Feasibility Randomised Trial
Secondary ID [1] 299375 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PRECeDe Pilot RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 314533 0
Gestational Diabetes 314534 0
Neonatal respiratory distress 314535 0
Transient tachypnoea of newborn 314536 0
caesarean section 314537 0
pregnancy 314538 0
neonatal hypoglycaemia 314539 0
Condition category
Condition code
Reproductive Health and Childbirth 312880 312880 0 0
Complications of newborn
Reproductive Health and Childbirth 312881 312881 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 312882 312882 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 312883 312883 0 0
Antenatal care
Reproductive Health and Childbirth 312884 312884 0 0
Breast feeding
Respiratory 312885 312885 0 0
Other respiratory disorders / diseases
Metabolic and Endocrine 312886 312886 0 0
Diabetes
Surgery 312998 312998 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
11.4 mg of Celestone Chrondose in 2ml (betamethasone 11.4 mg, as betamethasone sodium phosphate and betamethasone acetate)
2 injections will be administered intramuscularly, 24 hours apart, within 7 days prior to elective caesarean section, to participants randomised to receive the investigational product.
Intervention code [1] 315639 0
Prevention
Intervention code [2] 315887 0
Treatment: Drugs
Comparator / control treatment
Normal saline 2 mls in an identical appearing syringe.
2 injections will be administered intramuscularly, 24 hours apart, within 7 days prior to elective caesarean section, to participants randomised to receive the placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 321491 0
The proportion of all eligible women who consent and are randomised during the time period of the study.
Timepoint [1] 321491 0
Completion of recruitment
Secondary outcome [1] 375103 0
Rate of betamethasone use in eligible women outside of the study protocol assessed via data linkage to medical records
Timepoint [1] 375103 0
Up to time of elective caesarean section
Secondary outcome [2] 375104 0
Assessment of patient, treating obstetrician and treating neonatologist’s (for infants admitted to special care unit only) prediction of treatment allocation
Timepoint [2] 375104 0
Time of discharge of mother and / or infant from hospital
Secondary outcome [3] 375105 0
Time taken for research staff to screen, recruit, consent and randomise women.
Timepoint [3] 375105 0
Completion of Recruitment and Randomisation
Secondary outcome [4] 375106 0
Time taken for research staff to administer interventional products and collect outcome data following birth up to the time of discharge from hospital of mother and / or infant
Timepoint [4] 375106 0
Time of discharge from hospital of mother and / or infant
Secondary outcome [5] 375107 0
Time taken for research staff to follow up women and arrange completion of surveys at 6 weeks post-partum
Timepoint [5] 375107 0
At 6 weeks postpartum
Secondary outcome [6] 375108 0
Neonatal respiratory distress, defined as requiring admission to the neonatal nursery and any form of respiratory support (e.g. intermittent positive pressure via an endotracheal tube, nasal continuous positive airway pressure (CPAP), Hi- or Lo-flow oxygen/air mixture, or increased ambient oxygen delivered into an incubator) for 4 hours or longer. Data will be collected from the medical record.
Timepoint [6] 375108 0
4 hours following birth
Secondary outcome [7] 375109 0
Admission to neonatal nursery and length of stay. Data will be collected from the medical record and hospital administrative datasets.
Timepoint [7] 375109 0
Discharge from neonatal nursery
Secondary outcome [8] 375110 0
Severity of respiratory distress (defined as maximum appropriate mean airway pressure [MAP], and maximum appropriate fractional inspired oxygen [FiO2]) required to maintain oxygen saturations within the appropriate gestational range as measured by pulse oximetry.
Defined as a composite according to:
Mild: MAP <7.0 and / or FiO2 <0.40
Moderate: MAP 7.0 -9.9 and /or FiO2 0.40 to 0.79
Severe: MAP>/= 10.0 and / or FiO2 >0.80
Timepoint [8] 375110 0
Discharge from neonatal nursery
Secondary outcome [9] 375111 0
Need for and duration of any form of respiratory support (defined as intermittent positive pressure via an endotracheal tube, CPAP, Hi- or Lo-flow oxygen/air mixture, or increased ambient oxygen delivered into an incubator (including therapy required for less than 4 hours). Data will be collected from the medical record at the time of discharge from the nursery.
Timepoint [9] 375111 0
Discharge from neonatal nursery
Secondary outcome [10] 375112 0
Use of exogenous surfactant (prescribed and administered according to hospital medication chart
Timepoint [10] 375112 0
Discharge from neonatal nursery
Secondary outcome [11] 375113 0
Pneumothorax or air leak detected on chest radiograph requiring drainage
Timepoint [11] 375113 0
Discharge from neonatal nursery
Secondary outcome [12] 375114 0
Presence of x-ray features suggestive of hyaline membrane disease (independently adjudicated by a neonatal radiologist blinded to treatment allocation);
Timepoint [12] 375114 0
Discharge from neonatal nursery
Secondary outcome [13] 375115 0
Neonatal hypoglycaemia defined as any blood glucose concentration <2.6 mmol/l
Timepoint [13] 375115 0
Discharge from hospital
Secondary outcome [14] 375116 0
Neonatal hypoglycaemia defined as a blood glucose concentration <2.6mmol/l requiring treatment other than feeding (including dextrose gel, intravenous dextrose, glucagon).
Timepoint [14] 375116 0
Discharge from hospital
Secondary outcome [15] 375117 0
Requirement for additional insulin therapy for the mother to maintain fasting capillary blood sugars below 5.0mmol/l or post-prandial blood sugars below 6.7mmol/l, following administration of study drug prior to the caesarean section. Participants will be provided with a diary to record all blood sugar levels following administration of study drug or placebo. Participants will be provided with instructions to contact an endocrinologist if they have 2 consecutive fasting blood sugars above 5.0mmol/l or 2 consecutive postprandial blood sugars above 6.7mmol/l OR if a single blood sugar is above 8.0mmol/l.
Additional insulin doses will be recorded in the participant diary which will be collected at the time of the caesarean section.
Timepoint [15] 375117 0
At the time of the caesarean section
Secondary outcome [16] 375118 0
Highest maternal blood glucose concentration recorded between randomisation and birth. Maternal blood sugars will be tested at least prior to every meal and 2 hours after every meal.
Timepoint [16] 375118 0
Time of birth
Secondary outcome [17] 375119 0
Maternal infection from the time of randomisation up until 6 weeks postpartum including chorioamnionitis (defined as clinical signs of chorioamnionitis requiring intrapartum antibiotics); maternal pyrexia 38°C or higher; wound infection requiring antibiotic treatment; surgical / radiological drainage of wound collection. Data will be collected using a study specific questionnaire which will be completed either in person or via a telephone interview.
Timepoint [17] 375119 0
6 weeks post birth
Secondary outcome [18] 375120 0
Maternally reported side effects of antenatal corticosteroid or placebo injections (eg pain at injection site, nausea, headaches, changes in fetal movements). Side effects will be reported through the use of a study specific questionnaire with several side effects listed but women will also be invited to report any additional symptoms they notice.
Timepoint [18] 375120 0
Time of birth
Secondary outcome [19] 375121 0
Maternal mental health assessment using the Edinburgh Postnatal Depression scale (EPDS)
Timepoint [19] 375121 0
Baseline at randomisation and then 6 weeks post birth
Secondary outcome [20] 375122 0
Maternal general health prior to randomisation and at 6 weeks post partum using the SF36 and AQoL8D
Timepoint [20] 375122 0
Baseline at randomisation and then 6 weeks post birth
Secondary outcome [21] 375123 0
Breastfeeding rates at hospital discharge and 6 weeks post-partum based on maternal self report through a study specific survey. Data will be collected via either a face to face or telephone based interview.
Timepoint [21] 375123 0
Hospital discharge and 6 weeks post birth

Eligibility
Key inclusion criteria
Women with a singleton or twin pregnancy between 35+0 and 38+6 weeks who have pre-gestational diabetes OR gestational diabetes (diagnosed on a pregnancy 75g Oral glucose tolerance test according to the WHO criteria for gestational diabetes)
AND
plan to give birth by elective caesarean section within the next 7 days.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known major fetal anomaly or chromosomal anomaly.
2. Administration of any corticosteroid therapy within the last 7 days.
3. Contraindication to corticosteroids

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by internet / phone. A unique code will be generated. Pharmacy will dispense the appropriate medication according to the code and the randomisation sequence.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation generated by a computer with stratification according to:
Type of Diabetes - Type 1 Diabetes, Type 2 Diabetes, Gestational Diabetes
Gestation at time of Caesaean - 35+0 to 36+6 weeks, 37+0 to 38+6 weeks
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
The medication will be masked, however it is possible that staff administering the injections may be able to identify whether the syringe contains active ingredient or placebo since the active ingredient is a suspension while the placebo is a clear solution.
To maintain blinding, we will ensure that staff administering the injections do not disclose their suspicions about drug identity to the participant. Staff administering the drug will not be involved in the collection of any outcome data.
Endocrinologists may be required to adjust insulin doses for both the Active and Placebo group of participants. Hyperglycaemia is a common side effect of betamethasone. Endocrinologists will remain blinded to the treatment allocation but may be able to identify treatment allocation based on the presence or absence of maternal hyperglycaemia. Endocrinologists involved in managing maternal hyperglycaemia will not be involved in the collection or interpretation of outcome data.
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety
Statistical methods / analysis
As the feasibility study is not aiming to assess the efficacy of betamethasone in this setting, a significantly smaller sample size is required. A sample size of 50 would provide a representative sample of women to determine the primary outcome for the feasibility study, that is whether participation in a larger RCT is acceptable to women such that 30% of eligible women can be recruited to this study. This sample size is consistent with recommendations regarding sample size for feasibility studies.
We will undertake descriptive statistical analysis reporting the proportion of women screened, eligible, approached, consented and refused as well as the time taken to complete study procedures.
Outcomes will be compared between the intervention and control groups using an intention-to-treat analysis. For all binary outcomes the magnitude of the between-group differences will be quantified by fitting a logistic regression model to estimate the odds ratio (OR) and 95% confidence interval (CI) for the corresponding population OR, stratified by type of diabetes (Type 1 diabetes, Type 2 Diabetes, Gestational Diabetes), and gestation at planned elective CS. Linear regression will be used for non-categorical outcomes. For infant outcomes models will be fitted using Generalised Estimating Equations to allow for non-independence of outcomes among twins from the same pregnancy.

Recruitment
Recruitment status
Not yet 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)
VIC
Recruitment hospital [1] 14850 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 28109 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 303891 0
Hospital
Name [1] 303891 0
Maternal Fetal Medicine Research, Joan Kirner Women's & Children's Hospital
Address [1] 303891 0
Joan Kirner Women's & Children's Sunshine Hospital
176 Furlong Rd
St Albans, VIC 3021
Country [1] 303891 0
Australia
Primary sponsor type
Hospital
Name
Western Health
Address
176 Furlong Rd
St Albans, Victoria 3021
Country
Australia
Secondary sponsor category [1] 304037 0
None
Name [1] 304037 0
Address [1] 304037 0
Country [1] 304037 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304396 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 304396 0
Royal Melbourne Hospital
Level 2, South West
300 Grattan Street
Parkville Victoria, 3052
Ethics committee country [1] 304396 0
Australia
Date submitted for ethics approval [1] 304396 0
25/09/2019
Approval date [1] 304396 0
25/10/2019
Ethics approval number [1] 304396 0
HREC/57939/MH-2019

Summary
Brief summary
Administration of antenatal corticosteroids to women prior to preterm birth has been one of the greatest success stories of modern pregnancy and newborn care. Multiple studies have demonstrated a reduction in the rate of breathing problems in newborn babies after this treatment. More recently, several studies have reported benefits when antenatal corticosteroids are given to women who give birth by elective caesarean section after 35 weeks. Elective CS, as opposed to vaginal birth (or even CS in labour) is associated with greater risks of breathing problems in newborn infants and this results in longer hospital stays and separation from the mother. Women with diabetes were specifically excluded from the studies that have demonstrated improvements in the rate of newborn breathing problems, hence, whether these benefits are the same for infants born to women with diabetes is uncertain. Further research in the subgroup of women with diabetes during pregnancy is urgently needed.

This study has been designed to determine the feasibility of undertaking a much larger multicentre, randomised, placebo controlled trial to investigate the outcomes for the mother and baby following antenatal administration of corticosteroids within 7 days prior to elective CS in women with pre-gestational or gestational diabetes. A sample size of 2200 participants will be required for the larger trial. In order to determine the feasibility of such a large study and ensure the collection of appropriate outcome data, we are undertaking a smaller pilot feasibility trial to determine patient and clinician acceptability for such a trial.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96802 0
A/Prof Joanne Said
Address 96802 0
Maternal Fetal Medicine Unit
Joan Kirner Women's & Children's, Sunshine Hospital
176 Furlong Rd
St Albans, Victoria, 3021
Country 96802 0
Australia
Phone 96802 0
+61 3 9055 2400
Fax 96802 0
+61 3 9055 2165
Email 96802 0
jsaid@unimelb.edu.au
Contact person for public queries
Name 96803 0
A/Prof Joanne Said
Address 96803 0
Maternal Fetal Medicine Unit
Joan Kirner Women's & Children's, Sunshine Hospital
176 Furlong Rd
St Albans, Victoria, 3021
Country 96803 0
Australia
Phone 96803 0
+61 3 9055 2400
Fax 96803 0
+61 3 9055 2165
Email 96803 0
jsaid@unimelb.edu.au
Contact person for scientific queries
Name 96804 0
A/Prof Joanne Said
Address 96804 0
Maternal Fetal Medicine Unit
Joan Kirner Women's & Children's, Sunshine Hospital
176 Furlong Rd
St Albans, Victoria, 3021
Country 96804 0
Australia
Phone 96804 0
+61 3 9055 2400
Fax 96804 0
+61 3 9055 2165
Email 96804 0
jsaid@unimelb.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?
Individual, deidentified participant data underlying published results will be available
When will data be available (start and end dates)?
Beginning 12 months after publication up until 5 years after publication
Available to whom?
Researchers who provide a methodologically sound proposal at the discretion of the Principal Investigator and Sponsor
Available for what types of analyses?
IPD Meta-analyses
How or where can data be obtained?
By request to the Principal Investigator (email jsaid@unimelb.edu.au)
What supporting documents are/will be available?
Study protocol
Informed consent form
How or where can supporting documents be obtained?
Type [1] 5026 0
Study protocol
Citation [1] 5026 0
Link [1] 5026 0
Email [1] 5026 0
jsaid@unimelb.edu.au
Other [1] 5026 0
Attachment [1] 5026 0
Type [2] 5027 0
Informed consent form
Citation [2] 5027 0
Link [2] 5027 0
Email [2] 5027 0
jsaid@unimelb.edu.au
Other [2] 5027 0
Attachment [2] 5027 0
Summary results
No Results