Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001530112
Ethics application status
Approved
Date submitted
18/09/2019
Date registered
6/11/2019
Date last updated
1/12/2020
Date data sharing statement initially provided
6/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of treatment of obstructive sleep apnoea on the development of gestational diabetes in pregnancy (POSA).
Scientific title
A pilot randomised controlled trial on the effect of Continuous Positive Airway Pressure (CPAP) or positional therapy on the development of gestational diabetes in obstructive sleep apnoea in pregnancy.
Secondary ID [1] 299334 0
Nil
Universal Trial Number (UTN)
Trial acronym
POSA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 314480 0
Condition category
Condition code
Respiratory 312813 312813 0 0
Sleep apnoea
Metabolic and Endocrine 312958 312958 0 0
Diabetes
Reproductive Health and Childbirth 312959 312959 0 0
Fetal medicine and complications of pregnancy
Cardiovascular 312960 312960 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants with obstructive sleep apnoea will be allocated in randomly permuted blocks 1:1:1 to one of three groups
- Intervention 1 (CPAP) and usual care
- Intervention 2 (Positional therapy) and usual care
- Usual care alone

Participants will be allocated to use either CPAP or positional therapy after the results of their first diagnostic sleep study is known. In the CPAP group, initially participants will be commenced on auto-titrating CPAP (an auto-set) until a suitable fixed pressure is determined between 3-7 days after they start. The sleep technician will then change them to an appropriate fixed pressure, which will be the 90th percentile pressure derived from the auto-set machine. The fixed pressure range will be from 6-20cm water pressure.

The positional therpy device to be used is the "Nightshift" Positional Device. The device is a sensor attached to a silicone neck strap. The NightShift device uses vibrotactile feedback to discourage supine sleep. Downloaded data will provide compliance information associated with changes in sleep position and snoring.

The treatment will be administered an experienced CPAP therapist. Participants will be encouraged to use the treatment CPAP or positional therapy every night from when they are commenced on it, until when they deliver the baby. Adherence will be monitored through data downloads (device analytics) for both the CPAP and positional therapy groups when the participants are reviewed in the antenatal clinic.

The participants will be commenced on the treatment in the hospital clinic, but will use it at home .
Intervention code [1] 315603 0
Treatment: Devices
Comparator / control treatment
The control group will receive usual care in the form of regular antenatal visits
Control group
Active

Outcomes
Primary outcome [1] 321437 0
Gestational diabetes on oral glucose tolerance test
Timepoint [1] 321437 0
Oral glucose tolerance test at 28 weeks
Secondary outcome [1] 374939 0
Hypertensive disorder of pregnancy - this will be diagnosed based on clinical measurement in antenatal clinic with systolic blood pressure greater than 140 mm Hg or diastolic blood pressure of greater than 90 mm Hg. This will measured at least monthly, and more frequently if there are any concerns

If gestational hypertension is noted after 20 weeks, then all participants will be assessed for preeclampsia
Timepoint [1] 374939 0
Assessed for duration of pregnancy
Secondary outcome [2] 374940 0
Incident pre-eclampsia which wiil be assess based on the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) 2014 definition of preeclampsia, based on clinical, and haematological, and biochemical assessment – see list below

The definition of preeclampsia is based on the
Diagnosis of hypertension with SBP>140 or DBP>90 in conjunction with evidence of end organ damage as exemplified by one of the following.

Significant proteinuria (a spot urine protein/creatinine ratio greater than or equal to 30mg/mmol)
Increased PCR measured by spot urine test
Serum or plasma creatinine greater than 90 µmol/L - measured by blood test at any time

Thrombocytopenia less than 100,000 /µL - measured by blood test
Haemolysis (schistocytes or red cell fragments on blood film, raised bilirubin, raised lactate dehydrogenase greater than 600mIU/L, decreased haptoglobin) - measured by blood test
Disseminated intravascular coagulation - increased d-dimer and reduced fibrinogen measured by blood test
Uric acid - measured by blood test

Raised serum transaminases (Raised Ast, AlT) - measured by blood test
Severe epigastric and/or right upper quadrant pain – based on clinical assessment and noted in medical record with other causes of right upper quadrant pain excluded eg with abdominal ultrasound and foetal ultrasound to exclude an abruption

Neurological involvement
Convulsions (eclampsia) – based on clinical assessment and noted in medical record

Hyperreflexia with sustained clonus – based on clinical assessment and noted in medical record - more than two beats sustained clonus on repeated testing
Persistent new headache – based on clinical assessment and noted in medical record after all other clinical diagnoses have been excluded

Persistent visual disturbances (photopsia, scotomata, cortical blindness, posterior reversible encephalopathy syndrome, retinal vasospasm) – based on clinical assessment and noted in medical record after all other clinical diagnoses have been excluded

Stroke – based on CT scan

Pulmonary oedema – based on clinical examination (bibasal crepitations) and/or chest x-ray
Fetal growth restriction (FGR) - based on foetal ultrasound measurements as measured by the estimated foetal weight adjusted for weeks of gestation. Defined as less than the 10th centile of weight.

sPlt-1/PLGF ratio – based on blood tests gestation specific cut offs - if less than 32 weeks if the ratio is more than 85 and if more than 32 weeks the ratio must be more 110 but can’t be the only clinical finding
Timepoint [2] 374940 0
at the time it occurs during the pregnancy
Secondary outcome [3] 374941 0
Birthweight (kilograms and percentile).

Digital scales (Wedderburn) will be used to obtain this weight
Timepoint [3] 374941 0
Birth
Secondary outcome [4] 375284 0
Composite outcome of neonatal complications defined as outlined below
neonatal death, neonatal admission to ICU, length of admission into ICU, apgars <7 after 5 mins, arterial Ph<7, neonatal hypoglycaemia, infant respiratory distress syndrome, neonatal sepsis, neonatal meconium aspiration, neonatal hyperbilirubinaemia, neonatal persistent pulmonary hypertension, neonatal asphyxia, neonatal inguinal hernias

These outcomes will be measured as outlined below
neonatal death - dead or alive at the time of discharge
neonatal admission to ICU - admitted to NICU based on medical records.
length of admission into ICU - medical records and the babies discharge summary from the NICU
apgars <7 after 5 mins - assessed at birth by treating midwife or obstetrician usually, based on medical records

arterial pH<7 – foetal scalp blood gas if clinically indicated and if less than 7 very severe acideamia
neonatal hypoglycaemia - BSLs measures by foot prick in babies with mothers with gestational diabetes
infant respiratory distress syndrome, as defined by the NICU on the discharge summary
neonatal sepsis, as defined by ICU- sepsis with increased lactate
neonatal meconium aspiration - defined as respiratory distress in the newborn period due to the presence of meconium in the trachea based on medical records
neonatal hyperbilirubinaemia neonates that are jaundiced with an elevated total serum bilirubin adjusted for gestation as per SLHD jaundice guidelines that need any extra treatment like phototherapy ( see link to attached document) (https://www.slhd.nsw.gov.au/rpa/neonatal/content/pdf/guidelines/jaundice.pdf)
neonatal persistent pulmonary hypertension, defined as the failure of transition from foetal to neonatal circulation based on medical records
neonatal asphyxia defined as "an event or condition during the perinatal period that is likely to severely reduce oxygen delivery and lead to acidosis; and a failure of function of at least two organs (may include lung, heart, liver, brain, kidneys and hematological) consistent with the effects of acute asphyxia." based on medical records
neonatal inguinal hernias as diagnosed on baby check on discharge

Timepoint [4] 375284 0
The neonatal period is defined as one month post birth
Secondary outcome [5] 375286 0
Glycaemic control during pregnancy for participants who develop gestational diabetes based on the HbA1C
Timepoint [5] 375286 0
HbA1C checked
1. 28 weeks gestation
2. 36 weeks gestation
Secondary outcome [6] 375287 0
Maternal weight gain

Digital scales (Wedderburn) will be used to obtain this weight
Timepoint [6] 375287 0
For the duration of pregnancy, measured at antenatal visits which will occur monthly unless otherwise clinically inidcated
Secondary outcome [7] 375288 0
Circulating biomarkers (e.g. sFlt-1, PlGF, IL-6, TNFa, HIF1a)

The biomarkers are exploratory outcomes. sFL-1 gives us biochemical information about the degree of placental ischemia. PlGF relates to placental reserve and IL-6, TNFa relates to systemic inflammation potentially relates to systemic inflammation, HIF1a is peripheral marker of evolving placental hypoxia as a precursor to ischaemia.
Timepoint [7] 375288 0
1. 12-16 weeks gestation
2. two to six weeks later (average four weeks - 16-20 weeks gestation)
3. 28 weeks gestation
Secondary outcome [8] 375748 0
Uterine artery blood flow (pulsatility index measurements)
Timepoint [8] 375748 0
1. 12-16 weeks gestation
2. two to six weeks later (average four weeks - 16-20 weeks gestation)
3. 36 weeks gestation
Secondary outcome [9] 375749 0
Estimated foetal weight (grams) and percentile, calculated based on foetal ultrasound
Timepoint [9] 375749 0
1. 12-16 weeks gestation
2. two to six weeks later (average four weeks - 16-20 weeks gestation)
3. 36 weeks gestation

Eligibility
Key inclusion criteria
1. Early pregnancy (less than 14 weeks from last menstrual period)

2. Increased risk defined as ONE OR MORE of:
a. Body mass index greater than or equal to 35 kg/m2
b. Previous gestational diabetes mellitus (GDM)
c. Previous personal history of pre-eclampsia (or in mother or sister)
d. Underlying renal disease
e. Maternal type 2 diabetes (pre-gestational)
f. Symptoms of sleep-disordered breathing including snoring, witnessed apnoeas, mild excessive daytime sleepiness (which does not meet the criteria for severe excessive daytime sleepiness) or tiredness.
AND
g. Obstructive sleep apnoea diagnosed on in-lab polysomnography, based on the respiratory disturbance index (RDI) of greater than or equal to 5.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous diagnosis of sleep disordered breathing on active treatment
2. Confirmed GDM or pre-eclampsia
3. Maternal type 1 diabetes
4. Multifoetal gestation
5. Known foetal chromosomal abnormality
6. Inability to provide informed consent
7. Severe EDS based on clinical assessment (eg including a fall asleep MVA or near miss, transient sleepiness while driving/at lights or needing to pull over due to sleepiness while driving, or transient sleepiness in any other dangerous situation ie cooking, carrying baby) or Epworth Sleepiness Scale of greater than 15.

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)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
In this pilot study we plan to recruit 16 participants to the control and to each of the two intervention groups (i.e. 48 participants in total). This pilot is being performed to optimise the protocol and logistics for a larger trial. In addition, this pilot data will be used to apply for a larger scale grant in order to fund the larger randomized controlled trial (RCT).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
30/09/2019
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
30/09/2021
Actual
Sample size
Target
48
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14811 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 18130 0
Campbelltown Hospital - Campbelltown
Recruitment postcode(s) [1] 28061 0
2170 - Liverpool
Recruitment postcode(s) [2] 32123 0
2560 - Campbelltown

Funding & Sponsors
Funding source category [1] 303851 0
Government body
Name [1] 303851 0
South West Sydney Local Health District Womens Health Initiative Translational Unit (WHITU) academic unit
Country [1] 303851 0
Australia
Primary sponsor type
Government body
Name
South West Sydney Local Health District
Address
South West Sydney Local Health District
Liverpool Hospital
Locked bag 7103
Liverpool BC 1871
Country
Australia
Secondary sponsor category [1] 303982 0
None
Name [1] 303982 0
Address [1] 303982 0
Country [1] 303982 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304363 0
South West Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 304363 0
Ethics committee country [1] 304363 0
Australia
Date submitted for ethics approval [1] 304363 0
03/03/2019
Approval date [1] 304363 0
05/07/2019
Ethics approval number [1] 304363 0
2019/ETH00283

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

Contacts
Principal investigator
Name 96690 0
Dr Hima Vedam
Address 96690 0
Respiratory and Sleep Physician
Liverpool Hospital
Locked Bag 7103
Liverpool BC 1871
Country 96690 0
Australia
Phone 96690 0
+61 28738 3000
Fax 96690 0
Email 96690 0
[email protected]
Contact person for public queries
Name 96691 0
Hima Vedam
Address 96691 0
Respiratory and Sleep Physician
Liverpool Hospital
Locked Bag 7103
Liverpool BC 1871
Country 96691 0
Australia
Phone 96691 0
+61 28738 3000
Fax 96691 0
Email 96691 0
[email protected]
Contact person for scientific queries
Name 96692 0
Hima Vedam
Address 96692 0
Respiratory and Sleep Physician
Liverpool Hospital
Locked Bag 7103
Liverpool BC 1871
Country 96692 0
Australia
Phone 96692 0
+61 28738 3000
Fax 96692 0
Email 96692 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.