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Trial registered on ANZCTR


Registration number
ACTRN12616001372471
Ethics application status
Approved
Date submitted
3/08/2016
Date registered
4/10/2016
Date last updated
14/02/2019
Date data sharing statement initially provided
3/12/2018
Date results information initially provided
3/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
General Practice Optimising Structured MOnitoring To Improve Clinical outcomes in Type 2 Diabetes: An individually randomised trial of the effect of retrospective continuous glucose monitoring (rCGM) for people with type 2 diabetes in general practice on HbA1.
Scientific title
General Practice Optimising Structured MOnitoring To Improve Clinical outcomes in Type 2 Diabetes: An individually randomised trial of the effect of retrospective continuous glucose monitoring (rCGM) for people with type 2 diabetes in general practice on HbA1.
Secondary ID [1] 289500 0
NHMRC APP1104241
Universal Trial Number (UTN)
U1111-1184-4683
Trial acronym
The GP-OSMOTIC study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 299198 0
Condition category
Condition code
Metabolic and Endocrine 299206 299206 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
GP-OSMOTIC is a 2-arm individually randomised controlled trial (RCT) in general practice comparing collaborative retrospective Continuous Glucose Monitoring (r-CGM) to usual care in people with T2D on maximum non-insulin hypoglycaemic therapy and/or insulin whose HbA1c is out-of-target.

All participating General Practitioners (GPs) and Practice Nurses (PNs) will take part in a 2 hour training session, either on site at the practice or via an online video recording of the training. The training will be provided by a GP with a special interest in diabetes with minimum 5 years’ experience, a Registered Nurse-Credentialed Diabetes Educator with minimum 5 years’ experience and a health psychologist with expertise in diabetes self management and education. The training will involve a presentation about the rCGM device being used in the study (Abbott Libre Pro (c)), how to use the device and interpret the output, and will include a case-based discussion with role-playing vignettes )provided as short video clips) modelling a collaborative approach to consulting with patients and using the rCGM output in discussing treatment intensification.

Patients randomised to the intervention will attend an individual one-to-one, face-to-face Education Session of 60 minutes with the study Registered Nurse-Credentialed Diabetes Educator (RN-CDE). This will be held on-site at the patient's General Practice. This session will include instruction on how to wear the rCGM device being used (Abbott Libre Pro (c)) and how to interpret the glucose reports from the device in understanding diabetes self-management and in discussing treatment intensification with their GP. Brief supportive information about the device and about diabetes self-management (as commonly provided in diabetes education sessions) will be provided to patients.

Intervention patients will be asked to wear the rCGM device for a period of 2 weeks every 3 months ie at baseline, 3,6,9 and 12 months, as well as having an HbA1c at those times, and to consult with their GP and discuss the rCGM output glucose reports. This 3 monthly interval is in keeping with clinical practice guidelines about step wise regular consideration of treatment intensification. The rCGM device will be applied at those 3 monthly intervals by the GP clinic staff (ie the GP or Practice Nurse who have attended the health professional training). Patients and practices will be sent reminders to undertake this 3 monthly monitoring.

The training session for both health professionals and patients will cover collaborative interpretation of rCGM data in guiding treatment intensification. The aim of the training is to ensure that health professionals and patients have the knowledge, confidence and skills to work collaboratively to:
1. support the use of r-CGM;
2. interpret glucose patterns with a focus on
*fasting & postprandial levels,
*detecting hyper- and hypoglycaemia, and
*understanding glycaemic variability;
3. discuss behaviour change &
4. discuss treatment intensification, drawing on current evidence-based clinical guidelines.

Referral or consultation with an endocrinologist, CDE or any other appropriate health professional will be management options for GPs managing study patients
Intervention code [1] 295090 0
Treatment: Devices
Intervention code [2] 295811 0
Treatment: Other
Comparator / control treatment
Patients randomised to the control group will be managed according to usual clinical care. IE this means that following the baseline data collection these patients will be managed in the way their GP staff usually and routinely manage people with diabetes in that practice. GP and patient will however be prompted to undertake 3 monthly diabetes reviews in keeping with clinical practice guidelines about step wise regular consideration of treatment intensification

Patients randomised to the control group will also attend an education session with a local CDE (funded by the study if necessary to ensure financial barriers do not exist). We will assist with scheduling this for control group patients.

The 3-monthly review prompts and the one hour Diabetes Educator session for control patients will standardise these exposures across both arms allowing us to isolate the effect of the rCGM device used in the intervention group
Control group
Active

Outcomes
Primary outcome [1] 298687 0
Absolute difference in mean HbA1c at 12 months between the intervention and control arm. This is measured in a blood test. HbA1c measurement for any individual patient will be undertaken at the same pathology testing laboratory at baseline and 12 month follow up.
Timepoint [1] 298687 0
At 12 months after randomisation
Secondary outcome [1] 324969 0
Difference in mean percent time in target (4-10mmol/L) range at 12 months between the study groups (from data downloaded from the r-CGM device)
Timepoint [1] 324969 0
At 12 months after randomissation
Secondary outcome [2] 326359 0
Difference in mean diabetes-specific distress at 12 months between the study groups as measured by the Problem Areas in Diabetes (PAID) scale
Timepoint [2] 326359 0
At 12 months after randomisation
Secondary outcome [3] 366954 0
Incremental cost per quality-adjusted life year (QALY) for the intervention relative to control for the trial period, as measured by the EuroQol 5 dimension 3 levels (EQ-5D-3?L) .
Timepoint [3] 366954 0
12 months after randomisation
Secondary outcome [4] 366955 0
Difference in mean HbA1c (%) at 6 months between the intervention and control groups assessed by a blood test.
Timepoint [4] 366955 0
Six months after randomisation

Eligibility
Key inclusion criteria
1. Eligible practices / practitioners: General Practices in Victoria

2. Eligible patients: aged 18-80 years, Type 2 diabetes duration of >1 year and most recent HbA1c (in the previous 1 month) >7mmol/mol (0.5%) above their individualised target (based on age, duration of diabetes and complications) who are on at least two non-insulin hypoglycaemic therapy and/or insulin (therapy stable for the last 4 months).
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Debilitating medical condition (e.g. unstable CVD, severe mental illness, end-stage cancer), an eGFR<30 ml/min/1.73m2; proliferative retinopathy, pregnancy, lactating or planning pregnancy, unable to speak English/give informed consent, unwilling to use r-CGM or follow study protocol, allergy to adhesive tape, diagnosis of T2D within the past 12 months any condition that makes monitoring diabetes using HbA1c unreliable (e.g. haemoglobinopathy, iron deficiency anaemia).

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 is concealed.

Eligibility is determined by study staff after meeting with potentially eligible patients at their General Practice. Patients will not be allocated until after study consent is obtained, baseline data is collected and baseline r-CGM trace is started (i.e. sensor attached) at that meeting.

At that point, using an electronic radio-button in RedCAP (c) electronic contact is made with an allocation schedule developed "off-site" ie held at the University of Melbourne Deportment of General Practice.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
We will use block randomisation at the practice level. ie block randomisation sequences of 4 and 6 will be computer generated by the study statistician for each practice who participate and individual participating patients at each practice site will be randomised. .
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size has 80% power to detect a difference in mean HbA1c of 0.5% with a standard deviation of 1.3 and an alpha of 0.05. The required number of participants in each arm is therefore 108 ie a total of 216. Assuming a 20% attrition rate, this inflates to 270 (135 in each arm). Allowing for 10% clinic attrition and assuming 6 participants per clinic, this inflates to 50 clinics with 6 participants per clinic (150 in each arm). The minimum allowable number of participants in each clinic is 4.

Clinic, GP and patient characteristics at baseline will be summarised for each study group and assessed for imbalance. Mean HbA1c levels at baseline and 12 months will be plotted for each study arm.

A linear mixed effects model (i.e. with both fixed effect for treatment effect and baseline outcome measure and random effect for clinic) will be used to estimate the group difference in HbA1c using restricted maximum likelihood estimation with adjustment for baseline Hba1c. Any baseline characteristics that are imbalanced between study groups and associated with the outcome will also be adjusted for. The secondary analysis will examine whether the intervention effect differs between those with and without a history of hypoglycaemia. The same approach will be used to determine whether the intervention effect varies for those with a general HbA1c target compared to those with a personalised HbA1c target.

An intention to treat approach will be utilised where participants will be analysed according to the group they were assigned and in using a mixed effects model all participants will be included in the analysis. Reported measures will include the estimated mean HbA1c at 12 months for each study arm, the estimated mean difference in HbA1c between the two study arms, the estimated mean difference from target for each study arm and the estimated mean difference from target between the two groups.

Complier Average Causal Effect (CACE) Analysis
A complier average causal effect (CACE) analysis will be performed on the primary outcome to assess the size of the benefit of the intervention in those who comply with the intervention. Unlike a per protocol analysis (PP), CACE analysis preserves randomisation when estimating the intervention effect. This is achieved by comparing the mean HbA1c of ‘compliers’ in the intervention group with a similar group of control participants who would have complied if they were offered the intervention. The outcome of the analysis is the CACE effect which represents the difference in mean HbA1c between compliers in the intervention group and their counterpart compliers in the control group.

Definition of a complier for the CACE Analysis:
The following 4 requirements must be met for a participant to be considered a complier:
1. Participant attended the educational session at baseline with the study CDE
2. GP attended a face-to-face group education session or an education session with the study CDE or completed online training
3. Participant wore a CGM sensor at baseline, 3 months, 6 months and 9 months
4. Participant attended Clinic Assessment Visit (CAV) and discussed sensor trace at baseline, 3 months, 6 months and 9 months

The method assumes the same proportion of participants in the control group would have complied with the intervention if it was offered to them as those who did comply in the intervention group. Another important assumption is that mean HbA1c at 12 months is the same for non-compliers in both the intervention and control groups. It is this assumption that allows the mean HbA1c of the (expected) compliers in the control group to be calculated (using the observed mean HbA1c in the control group). The CACE effect is then calculated as the difference in mean HbA1c between actual compliers in the intervention group and expected compliers in the control group.

Sensitivity analysis
Under the mixed effects model, the missing data are assumed to be missing at random. Under this assumption, the difference between the mean of the missing data and the mean of the observed data d, is zero. To test the robustness of the regression results in the absence of randomly missing data, a sensitivity analysis will be performed whereby plausible values for d other than 0 will be considered. Positive values of d indicate that on average, participants with missing data have higher (worse) HbA1c than observed participants and negative values of d assume participants with missing data have lower (better) mean HbA1c than observed participants. Regression results for plausible values of d will be analysed to determine whether study conclusions change in the absence of the missing at random assumption.

Recruitment
Recruitment status
Completed
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

Funding & Sponsors
Funding source category [1] 293872 0
Government body
Name [1] 293872 0
National Health and Medical Research Council
Address [1] 293872 0
GPO Box 1421

Canberra ACT 2601
Country [1] 293872 0
Australia
Funding source category [2] 293873 0
Commercial sector/Industry
Name [2] 293873 0
Sanofi-Aventis Australia
Address [2] 293873 0
Talavera Corporate Centre, Building D, 12-24 Talavera Road, Macquarie Park NSW 2113
Country [2] 293873 0
Australia
Funding source category [3] 293874 0
Commercial sector/Industry
Name [3] 293874 0
Abbott Diabetes Care
Address [3] 293874 0
Abbott Diabetes Care
Range Road
Witney, OX29 0YL, UK
Country [3] 293874 0
United States of America
Primary sponsor type
Individual
Name
John Furler
Address
Department of General Practice, University of Melbourne,
200 Berkeley Street
Carlton
Victoria 3053
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 293491 0
None
Name [1] 293491 0
Address [1] 293491 0
Country [1] 293491 0
Other collaborator category [1] 279245 0
University
Name [1] 279245 0
Professor James Best
Address [1] 279245 0
Lee Kong Chian School of Medicine
Country [1] 279245 0
Singapore
Other collaborator category [2] 279246 0
University
Name [2] 279246 0
Professor David O'Neal
Address [2] 279246 0
University of Melbourne
Country [2] 279246 0
Australia
Other collaborator category [3] 279247 0
University
Name [3] 279247 0
Professor Jane Speight
Address [3] 279247 0
Deakin University
Country [3] 279247 0
Australia
Other collaborator category [4] 279248 0
University
Name [4] 279248 0
Professor Irene Blackberry
Address [4] 279248 0
La Trobe University
Country [4] 279248 0
Australia
Other collaborator category [5] 279249 0
University
Name [5] 279249 0
Professor Kamlesh Khunti
Address [5] 279249 0
Leicester University
Country [5] 279249 0
United Kingdom
Other collaborator category [6] 279250 0
University
Name [6] 279250 0
Dr Kim Dalziel
Address [6] 279250 0
University of Melbourne
Country [6] 279250 0
Australia
Other collaborator category [7] 279251 0
University
Name [7] 279251 0
Professor Danny Liew
Address [7] 279251 0
Monash University
Country [7] 279251 0
Australia
Other collaborator category [8] 279252 0
University
Name [8] 279252 0
Clinical Associate Professor Mark Kennedy
Address [8] 279252 0
University of Melbourne
Country [8] 279252 0
Australia
Other collaborator category [9] 279253 0
University
Name [9] 279253 0
Clinical Associate Professor Ralph Audehm
Address [9] 279253 0
University of Melbourne
Country [9] 279253 0
Australia
Other collaborator category [10] 279254 0
University
Name [10] 279254 0
Professor Alicia Jenkins
Address [10] 279254 0
University of Sydney
Country [10] 279254 0
Australia
Other collaborator category [11] 279255 0
University
Name [11] 279255 0
Professor Philip Clarke
Address [11] 279255 0
University of Melbourne
Country [11] 279255 0
Australia
Other collaborator category [12] 279256 0
University
Name [12] 279256 0
Dr Jo-Anne Manksi-Nankervis
Address [12] 279256 0
University of Melbourne
Country [12] 279256 0
Australia
Other collaborator category [13] 279257 0
University
Name [13] 279257 0
Dr Jessica Browne
Address [13] 279257 0
Deakin University
Country [13] 279257 0
Australia
Other collaborator category [14] 279909 0
University
Name [14] 279909 0
Dr Elizabeth Holmes-Truscott
Address [14] 279909 0
Deakin University
Country [14] 279909 0
Australia
Other collaborator category [15] 279910 0
University
Name [15] 279910 0
Dr Malcolm Clarke
Address [15] 279910 0
University of Melbourne
Country [15] 279910 0
Australia
Other collaborator category [16] 280324 0
Individual
Name [16] 280324 0
Max Catchpool
Address [16] 280324 0
Health Economics Unit, Centre for Health Policy | Melbourne School of Population and Global Health
Level 4, 207 Bouverie Street
The University of Melbourne, Victoria 3010 Australia
Country [16] 280324 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295292 0
Health Sciences Human Ethics Sub Committee
Ethics committee address [1] 295292 0
Office for Research Ethics and Integrity
The University of Melbourne
Level 3, 780 Elizabeth Street
Vic. 3010
Ethics committee country [1] 295292 0
Australia
Date submitted for ethics approval [1] 295292 0
01/06/2016
Approval date [1] 295292 0
13/07/2016
Ethics approval number [1] 295292 0
1647151

Summary
Brief summary
Our aim is to test the effect of a new wearable device (a continuous glucose monitor) on the achievement of evidence-based targets for overall glucose levels (glycemic targets).

The general way of measuring glycaemic targes is to measure HbA1C in the blood, which gives an average of the glucose levels over the last 3 mths. Based on this measure about half of people with T2D in the community are not in the glycemic target of 53 mmol/mol.. We think knowing more about the day-to-day variation in glucose levels may be important, because that sort of information might help GP and patient to make more personalised and rational changes in treatment (including lifestyle changes and medicines).

Our research question are:
1. Does the judicious use of intermittent retrospective continuous glucose monitoring (r-CGM) in primary care improve glycaemic control as measured by HbA1c?
2. Is intermittent r-CGM cost-effective?

This is an individually randomised controlled trial set in General Practices in Victoria. Up to 60 practices and up to 300 patients will participate. Eligible patients are people with T2D who are out of glycaemic target despite moderately intensive therapy. People will be asked to complete a survey and have a blood test at the beginning and at 12 months. Patients randomised to the intervention group are asked to wear the r-CGM device every three months for a period of 2 weeks then to meet their GP to discuss it. Patients in the control group just continue to have usual diabetes care.
Trial website
http://medicine.unimelb.edu.au/research-groups/general-practice-research/diabetes-and-cardio-metabolic-conditions/general-practice-optimising-structured-monitoring-to-improve-clinical-outcomes-in-type-2-diabetes-gp-osmotic-t2d
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66790 0
A/Prof John Furler
Address 66790 0
Department of General Practice
University of Melbourne
200 Berkeley St
Carlton VIC 3053
Country 66790 0
Australia
Phone 66790 0
+61 3 83444747
Fax 66790 0
Email 66790 0
j.furler@unimelb.edu.au
Contact person for public queries
Name 66791 0
A/Prof John Furler
Address 66791 0
Department of General Practice
University of Melbourne
200 Berkeley St
Carlton VIC 3053
Country 66791 0
Australia
Phone 66791 0
+61 3 83444747
Fax 66791 0
Email 66791 0
j.furler@unimelb.edu.au
Contact person for scientific queries
Name 66792 0
A/Prof John Furler
Address 66792 0
Department of General Practice
University of Melbourne
200 Berkeley St
Carlton VIC 3053
Country 66792 0
Australia
Phone 66792 0
+61 3 83444747
Fax 66792 0
Email 66792 0
j.furler@unimelb.edu.au

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?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary