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Trial registered on ANZCTR


Registration number
ACTRN12617000359336
Ethics application status
Approved
Date submitted
5/03/2017
Date registered
8/03/2017
Date last updated
28/01/2020
Date data sharing statement initially provided
29/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of the impact of insulin pump therapy, augmented with continuous glucose monitoring, on outcomes for mother and baby, in pregnant women with Type 1 diabetes when compared to conventional treatment with insulin pump therapy alone or multiple daily insulin injections.
Scientific title
Comparison of Sensor Augmented Insulin Pump (with Smartguard technology) (SAP) with Non Augmented Pump Therapy (CSII) and Multiple daily injections (MDI) on Maternal and Neonatal Outcomes in Pregnancy in Women with Type 1 Diabetes.
Secondary ID [1] 291218 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
TYpe 1 Diabetes Mellitus 302136 0
Pregnancy 302137 0
Condition category
Condition code
Metabolic and Endocrine 301748 301748 0 0
Diabetes
Reproductive Health and Childbirth 301749 301749 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants with type 1 diabetes and plans for pregnancy or currently pregnant (first trimester) will be recruited from preconception clinics, diabetes clinics and diabetes in pregnancy clinics. Women will be offered involvement in the intervention arm if they unable to achieve a target HbA1c of 6.5% or less on current therapy, or are acheiving HbA1c target but with significant hypoglycaemia. They must be willing to undertake education involved for adequate CSII and CGMS use.

The primary intervention involves the use of a sensor augmented Minimed 640G insulin pump with predictive suspend before low/SmartGuard feature. Components of this intervention include:
1. The Minimed 640G insulin pump will be offered on loan to women either preconception or early pregnancy (before 12 weeks gestation) if they meet inclusion criteria. Pump therapy will continue for the duration of pregnancy to 4 weeks post partum, at which point they will be supported to transition back to multiple daily injections. Women will receive information and support about how to access their own pump during pregnancy in case they wish to pursue this as ongoing therapy after returning the loan pump.

2. CGMS that involves the subcutaneous insertion of an Enlite sensor that continuously communicates interstitial glucose readings to the Minimed 604G pump. Women will be able to see their blood sugars 'real time'. Women will be required to calibrate their CGMS by taking 3-4 fingerprick blood glucose levels per day.
Women in the intervention arm will be offered sensors for continuous use with their pumps in the first and third trimester, peri/post partum and also if they are admitted with a diagnosis of preeclampsia. They will return to conventional monitoring with 4-6 daily fingerprick blood glucose measurements in the second trimester.

3. Use of the SmartGuard feature of the Minimed 640G insulin pump. This feature uses an algorithm to predict hypoglycaemia within the next 30 minutes and suspends insulin delivery to prevent reaching the low threshold. This feature will be set up for use with the sensor at each of the above time points aiming to potentiate tighter glycaemic control with fewer hypoglycaemic episodes.

Women in the intervention arm will be offered extra individual, face to face appointments prior to and soon after starting the SAP therapy. These include:
1. Up to 3 additional dietician appointments (for up to 1 hour each) for education about carbohydrate counting (by dietician with over 10 years experience). Women will be given summary hand outs and recommendations about reference guides (mobile phone applications and books) that may be helpful for further information.

2. Up to 4 additional appointments (up to 1 hour each) with a credentialed diabetes educator (with over 10 years experience) to learn use of the Minimed 640G insulin pump and CGMS use and to set up the SmartGuard feature. Women will be given summary hand outs and instruction manuals that may be helpful to troubleshoot any issues with the pump and/or CGMS if required. Phone support will also be offered if needed.

The Minimed 640G pump will be downloaded:
1. By the CDE at each appointment review (endocrinologist/CDE/Dietician).
2. By the participant from their home computer between appointments and reviewed by the treating study team.

At each download, the patient will receive suggestions about changes to insulin pump settings to optimise glycaemia (either face to face or via phone and/or email).

All women will receive routine care in pregnancy to optimise their diabetes and reduce risk of potential pregnancy adverse outcomes, including regular review for titration of their insulin pump settings. They will be offered usual antenatal care including routine scans (nuchal translucency, morphology and regular growth and well being scans in the third trimester).

They will be requested to undertake a Diabetes Quality of Life Questionnaire prior to starting insulin pump therapy and repeat it at the end of the first trimester.
Intervention code [1] 297226 0
Treatment: Devices
Comparator / control treatment
Prospective participants:
Participants with type 1 diabetes and plans for pregnancy or currently pregnant (first trimester) will be recruited from the preconceptions clinics, diabetes clinics and diabetes in pregnancy clinics. If women are meeting the target HbA1c of 6.5% or less on current therapy without significant hypoglycaemia and/or are unwilling to undertake education involved for use of a sensor augmented pump, they will be offered inclusion in one of two control arms.

1. Women on CSII - Control group 1:
Women already on CSII with good control/no signficiant hypoglycaemia will continue continue usual insulin pump therapy. They will receive regular review of their insulin pump settings as per usual care in pregnancy.

The primary intervention will be CGMS using an iPro system. It involves the subcutaneous insertion of an Enlite sensor with a transmitter that records and stores five minutely interstitial glucose readings for up to 6 days. The readings will not be available 'real time' and women will continue taking their usual fingerprick blood glucose readings. The transmitter will be downloaded at the end of the 6 day period and reviewed by the endocrinologist with the participant.

The benefit of using this 'blinded' sensor is the increased information provided - i.e. instead of the conventional 4-6 blood glucose readings per day (maximum 36 per 6 day period) available to guide insulin pump setting changes, there will be 288 readings per day (maximum 1728 for the 6 day lifetime of the sensor) to help titrate pump settings. Otherwise unrecognised periods of hypo and hyperglycaemia may be diagnosed and targeted. This is not part of standard care in pregnancy but may be undertaken in pregnancy at the discretion of the treating endocrinologist if there are concerns about glycaemic control without a cause being determined from available blood glucose records.

Women will be offered a 'blinded' sensor at 8, 28, 36 weeks gestation, at delivery/early post partum and if admitted with pre eclampsia.

2. Women on Multiple Daily Injection (MDI) - Control group 2:
Women on conventional therapy of up to five daily injections of insulin with good control/no signficiant hypoglycaemia will continue this therapy. They will receive regular review of their insulin doses to optimise glycaemia as per usual care in pregnancy.

As per the CSII control group, the primary intervention will be CGMS using an iPro system. It involves the subcutaneous insertion of an Enlite sensor with a transmitter that records and stores five minutely interstitial glucose readings for up to 6 days. The readings will not be available 'real time' and women will continue taking their usual fingerprick blood glucose readings. The transmitter will be downloaded at the end of the 6 day period and reviewed by the endocrinologist with the participant.

The benefit of using this 'blinded' sensor is the increased information provided - i.e. instead of the conventional 4-6 blood glucose readings per day (maximum 36 over a 6 day period) available to guide insulin dose changes, there will be 288 readings per day (maximum 1728 for the 6 day lifetime of the sensor) to help titrate doses. Otherwise unrecognised periods of hypo and hyperglycaemia may be diagnosed and targeted.

They will be offered a blinded sensor at 8, 28, 36 weeks gestation, at delivery/early post partum and if admitted with pre eclampsia.

All women will receive routine care in pregnancy to optimise their diabetes and reduce risk of potential pregnancy adverse outcomes, including regular review for titration of their insulin doses. They will be offered usual antenatal care including routine scans (nuchal translucency, morphology and regular growth and well being scans in the third trimester).

They will be requested to undertake a Diabetes Quality of Life Questionnaire pre and post starting insulin pump therapy.

Retrospective participants:
3. Historical Controls - Control group 3:
Women who have type 1 diabetes and have previously delivered a baby in the Sunshine Coast Hospital and Health Service (SCHHS) between 2013-2016.

To enable a robust comparison of study outcomes and enable real world benchmarking, up to 24 women with Type 1 diabetes and pregnancy seen in the SCHHS between 2013-2016 (prior to the start of this study) will be identified via DRG coding for inclusion in the historical control group. A retrospective chart review will be undertaken to collect all data points as per the prospective groups with the exception of glycaemic variability and time spent out of target range (due to lack of continuous glucose monitoring) and patient satisfaction surveys.
Control group
Active

Outcomes
Primary outcome [1] 301156 0
Composite primary outcome of glycaemic control as defined by:
1. Percent time spent in target glucose range (Australian Diabetes In Pregnancy Society defined 4-8 mmol/L).
2. Percent time spent in hyperglycaemic range (>8mmol/L).
3. Percent time spent in hypoglycaemic range (<4mmol/L).

These parameters will be assessed using data from continuous glucose monitoring. The sensors will be worn continuously in the first and third trimesters and peri/post partum with real time interstitial glucose data available to the women in the intervention group. The two control groups will wear a single blinded sensor (expected to last 6 days) at 8, 28 and 36 weeks gestation and peripartum, with data downloaded from the device at the end of use. Percent time will be calculated using the sum of the minutes spent in each range as a percentage of the total time recorded.

Further data regarding glycaemia will be collected from download of blood glucose monitors in the intervention arm (second trimester) and control groups.
Timepoint [1] 301156 0
Assessed at the end of each trimester and 4 weeks post partum.
Primary outcome [2] 301301 0
Glycated haemoglobin (HbA1c). This will be measured monthly using point of care testing.
Timepoint [2] 301301 0
Third monthly preconception and monthly during pregnancy.
Primary outcome [3] 301385 0
Patient satisfaction with treatment of diabetes - assessed using the Diabetes Quality of Life Questionnaire (Diabetes and Complications Control Trial (DCCT) study group and validated in Type 1 and 2 diabetes).
Timepoint [3] 301385 0
At the end of first trimester.
Secondary outcome [1] 332270 0
Severity of hypoglycaemia.
Mild events defined as being managed by the patient alone with oral carbohydrate.
Severe events defined as requiring help from another person to administer oral carbohydrate, injection of glucagon or glucose in order to restore the blood glucose level.

Data regarding severity of hypoglycaemia will be collected from patient self reporting and linked to CGM/blood glucose meter data where available.
This will be assessed as a primary outcome.
Timepoint [1] 332270 0
At the end of each trimester and 4 weeks post partum.
Secondary outcome [2] 332317 0
Total gestational weight gain.

Pre pregnancy weight will be recorded at the first visit. If a women is recruited when pregnant, her first recorded pregnancy weight will be used as baseline and correlated with self reported pre pregnancy weight. If these are significantly different, early pregnancy weight will be used as default.

Weights will be recorded at every visit up to delivery. Final weight will be as that recorded after 36 weeks and as close as possible to delivery.

Total gestational weight gain will be calculated as the difference between the initial weight and final visit weights .
Timepoint [2] 332317 0
At completion of pregnancy.
Secondary outcome [3] 332334 0
Complications of pregnancy.

Information will be collected from the medical records. Complications could include miscarriage, hypertensive disorders of pregnancy, pre term delivery and polyhydramnios.
Timepoint [3] 332334 0
At the end of each trimester and 4 weeks post partum.
Secondary outcome [4] 332521 0
Mode of delivery.

Information will be collected from the medical records.

Timepoint [4] 332521 0
At delivery/completion of pregnancy.
Secondary outcome [5] 332525 0
Gestational age at delivery.

Information will be collected from direct patient review peridelivery and/or medical record.
Timepoint [5] 332525 0
At delivery/completion of pregnancy.
Secondary outcome [6] 332526 0
Birthweight of baby.

Information will be collected from direct patient review and/or medical records.
Timepoint [6] 332526 0
At delivery/completion of pregnancy.
Secondary outcome [7] 332527 0
Breast feeding rates.

Women will self report breastfeeding practices (exclusive/mixed/not breastfeeding) at a 4 week review post partum.
Timepoint [7] 332527 0
Four weeks post partum.
Secondary outcome [8] 332529 0
Neonatal complications.

Information will be collected from medical records and may include neonatal hypoglycaemia, jaundice and admission to special care nursery.
Timepoint [8] 332529 0
Four weeks post partum.
Secondary outcome [9] 332530 0
Maternal complications of diabetes.

Information will be collected from medical records including new/progressive retinopathy and nephropathy.
Timepoint [9] 332530 0
At the end of each trimester and 4 weeks post partum.
Secondary outcome [10] 366232 0
Economic Analysis of resource utilisation.
An evaluation of cost differences between the intervention and control cohorts will be conducted using de-identified patient level cost and outcome data.
Cost estimates will be determined for each group, including out of pocket costs for participants (based on equipment usage/technology costs), health service outpatient visits and inpatient length of stays (hospital medical records).
Outcomes will then be extrapolated to estimate likely cost outcomes under a scenario where the technology were utilised across its full usable life (i.e. continuous use over four years).
Timepoint [10] 366232 0
At completion of study.

Eligibility
Key inclusion criteria
1. Women with Type 1 diabetes who are preconception (planning pregnancy but not yet pregnant) or in early pregnancy (less than 12 weeks gestation) who currently administer insulin.

2. Criteria for intervention:
i. Inability to achieve target HbA1c (<6.5%) or having significant hypoglycaemia using conventional treatment with multiple daily injections;
ii. Women who can demonstrate willingness and ability to carbohydrate count and undertake the required education to use insulin pump therapy;
iii. Women who are willing to enter into an agreement/contract outlining: a) that they will be responsible for the insulin pump consumables (cannulae, infusion sets and reservoirs) for the duration of the pump loan (approx. $30/month); b) that there will be a 3 month trial period where they will need to meet criteria (including appropriate education, ability to use the pump, improvement in predefined glycaemic parameters) for ongoing use of a loan pump; c) that the pump will be loaned until up to 4 weeks postdelivery, after which the pump will be returned to the department.
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women not planning pregnancy.

2. Women presenting after 12 weeks gestation.

3. Exclusion from intervention includes women not demonstrating willingness to undertake appropriate education or accept conditions of loan of pump.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This pilot study will include 78 patients including 54 prospectively recruited patients and 24 historical controls. There is currently limited published data from which to perform a power calculation. The data from this pilot will inform the power calculation for a potentially larger study.
However, a power calculation can be based on the outcome of time spent outside glycaemic target range. It has been shown that women with Type 1 diabetes spend, on average 50% of the time in pregnancy out of the target range for glycaemia. We expect SAP therapy to halve this.
To demonstrate a reduction in time out of range from 50% to 25% using SAP therapy would require a minimum sample size of 29 subjects (alpha 0.05, beta 0.20)
Patient satisfaction and quality of life will be assessed with the validated Diabetes Quality of Life Score. A mean of the total score, and means of each of the four primary scales will be calculated. The scores will be compared before and after starting the pump in the SAP intervention group and also between the SAP and control groups using the Wilcoxon signed rank test.
Of the remaining variables - continuous variables will be analysed using standard Student’s t-test for paired or unpaired, and categorical variables using the Fisher’s exact test. In all statistical comparisons, p<0.05 will be considered as significant.
A costing analysis will compare health service utilisation and outcomes between intervention and control cohorts. The costs of the technology and consumable requirements for each cohort will be presented alongside potential cost offsets including the number of maternal clinic visits/reviews, maternal hospital admission rates and length of stay and Special Care Nursery requirement and length of stay.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
22/03/2017
Actual
22/03/2017
Date of last participant enrolment
Anticipated
22/03/2022
Actual
Date of last data collection
Anticipated
22/12/2022
Actual
Sample size
Target
78
Accrual to date
57
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 10068 0
Sunshine Coast University Hospital - Birtinya
Recruitment postcode(s) [1] 21593 0
4575 - Birtinya

Funding & Sponsors
Funding source category [1] 295668 0
Government body
Name [1] 295668 0
Queensland Health - New Technology Funding and Evaluation Program
Country [1] 295668 0
Australia
Funding source category [2] 295807 0
Charities/Societies/Foundations
Name [2] 295807 0
Wishlist
Country [2] 295807 0
Australia
Primary sponsor type
Individual
Name
Dr Sophie Poulter
Address
Endocrinology Department
Sunshine Coast University Hospital
6 Doherty St
Birtinya
Queensland
4575
Country
Australia
Secondary sponsor category [1] 294515 0
Hospital
Name [1] 294515 0
Sunshine Coast University Hospital
Address [1] 294515 0
6 Doherty St
Birtinya
Queensland
4575
Country [1] 294515 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296983 0
Royal Brisbane Hospital
Ethics committee address [1] 296983 0
HREC
Level 7, Block 7
Royal Brisbane and Women's Hospital
Herston
Queensland
4029
Ethics committee country [1] 296983 0
Australia
Date submitted for ethics approval [1] 296983 0
23/09/2016
Approval date [1] 296983 0
12/12/2016
Ethics approval number [1] 296983 0
HREC/16/QRBW/490

Summary
Brief summary
This study aims to determine the benefit of using sensor augmented insulin pump (with a predictive suspend before low feature) therapy to determine if tighter control of diabetes with less hypoglycaemia can be achieved and have an impact on maternal and foetal outcomes when compared to non sensor augmented pump therapy and multiple daily injections in pregnant women with type 1 diabetes. Outcomes will be benchmarked against historical outcomes in women with Type 1 diabetes in pregnancy who have delivered in the hospital and health service prior to the study.

It will assess if women using this therapy are more satisfied with their treatment, whether it has an impact on other maternal and foetal outcomes and economic implications for the use of this technology.

The study will generate data about glycaemia and insulin requirements after diagnosis of pre eclampsia, during labour and early breastfeeding.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72618 0
Dr Sophie Poulter
Address 72618 0
Endocrinology Department
Sunshine Coast University Hospital
6 Doherty St
Birtinya
Queensland
4574
Country 72618 0
Australia
Phone 72618 0
+61 7 5470 6099
Fax 72618 0
+61 7 5470 5839
Email 72618 0
[email protected]
Contact person for public queries
Name 72619 0
Sophie Poulter
Address 72619 0
Endocrinology Department
Sunshine Coast University Hospital
6 Doherty St
Birtinya
Queensland
4575
Country 72619 0
Australia
Phone 72619 0
+61 7 5470 6099
Fax 72619 0
+61 7 5470 5839
Email 72619 0
[email protected]
Contact person for scientific queries
Name 72620 0
Sophie Poulter
Address 72620 0
Endocrinology Department
Sunshine Coast University Hospital
6 Doherty St
Birtinya
Queensland
4575
Country 72620 0
Australia
Phone 72620 0
+61 7 5470 6099
Fax 72620 0
+61 7 5470 5839
Email 72620 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
Confidential and sensitive data regarding pregnancy and offspring collected.


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.