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Trial registered on ANZCTR


Registration number
ACTRN12615000732583
Ethics application status
Approved
Date submitted
4/07/2015
Date registered
16/07/2015
Date last updated
16/07/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Stop or Replace: Effect of stopping sulfonylureas or replacing sulfonylureas with a dipeptidyl peptidase 4 (DPP-IV) inhibitor in Type 2 diabetes patients on pre-mix insulin.
Scientific title
STop Or REplace – STORE: Patients with type 2 diabetes on pre-mix insulin: Impact of stopping sulfonylureas or of replacing sulfonylureas with a DPP-IV Inhibitor on glycaemic control, hypoglycaemia and body weight.
Secondary ID [1] 287041 0
NIL
Universal Trial Number (UTN)
Trial acronym
STORE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 2 diabetes 295512 0
Condition category
Condition code
Metabolic and Endocrine 295773 295773 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Prospective, randomised, open label, controlled trial with three arms
1.) Patients continue Sulfonylurea (oral tablet, no change in product, dose or frequency)
2.) Patients stop Sulfonylurea
3.) Patients replace Sulfonylurea with the DPP4 inhibitor Linagliptin (oral tablet, 5mg/day)
Study duration: 6 months
Other medications (for diabetes or other conditions) will be continued.
Adherence will be monitored by pill count of returned tablets at follow-up visits
Intervention code [1] 292252 0
Treatment: Drugs
Comparator / control treatment
Patients randomised to continue sulfonylureas will act as the control arm. They will take at least one sulfonylurea class drug at the dose that they would normally take for diabetes management under standard care.
Control group
Active

Outcomes
Primary outcome [1] 295480 0
To measure the change in glycaemic control when stopping SU or replacing SU with a DPP-4 inhibitor in patients on pre-mix insulin. This will be assessed by:
a) HbA1c
b) 4-point capillary blood glucose measurements done by patients at home, at least 7 continuous days preceding the appointment.
Timepoint [1] 295480 0
Outcomes will be assessed at 3 and 6 months and compared to baseline measures.
Secondary outcome [1] 315670 0
Changes in body weight (weight gain is a common side side effects of sulfonylureas).
This will be assessed by measuring body weight by the same calibrated hospital scale at the time of each study visit.
Timepoint [1] 315670 0
These outcomes will be assessed at 3 and 6 months and compared to baseline measures.
Secondary outcome [2] 315771 0
Frequency and severity of hypoglycaemic episodes.
This will be assessed by standard questions to the patients as well as review of the patient's blood glucose diary at the time of study visit.
Timepoint [2] 315771 0
These outcomes will be assessed at 3 and 6 months and compared to baseline measures.

Eligibility
Key inclusion criteria
- Diagnosed with type 2 diabetes
- Taking sulfonylurea since > 4 years
- Taking NovoMix30 or HumalogMix25 at least twice daily since more than 6 months
- Stable dose of current regular medication in last 4 weeks
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- HbA1c > 8.5%
- Already on DPP-4 inhibitor
- Intolerance or contraindication to DPP-4 inhibitors
- Unstable micro- or macrovascular complications within last 3 months
- Non-adherence to medications or glucose monitoring
- Type 1 diabetes

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)
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
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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)
NSW
Recruitment hospital [1] 4003 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst

Funding & Sponsors
Funding source category [1] 291596 0
Hospital
Name [1] 291596 0
St Vincent's Hospital Sydney
Address [1] 291596 0
390 Victoria Street, Darlinghurst NSW 2010
Country [1] 291596 0
Australia
Funding source category [2] 291597 0
Commercial sector/Industry
Name [2] 291597 0
Competitive Grant from Regional Diabetes Support Scheme, Novo Nordisk
Address [2] 291597 0
Novo Nordisk Pharmaceuticals Pty. Ltd.
PO Box 7586
Baulkham Hills Business Centre NSW 2153
Australia
Country [2] 291597 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Sydney
Address
390 Victoria Street, Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 290268 0
None
Name [1] 290268 0
Address [1] 290268 0
Country [1] 290268 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293127 0
St Vincent's Hospital HREC
Ethics committee address [1] 293127 0
St Vincent's Hospital
Research Office
L6 De Lacey Building
390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 293127 0
Australia
Date submitted for ethics approval [1] 293127 0
02/02/2015
Approval date [1] 293127 0
05/06/2015
Ethics approval number [1] 293127 0
HREC/15/SVH/34

Summary
Brief summary
The emerging epidemic of type 2 diabetes, coupled with finite health resources, requires the treatment of hyperglycaemia to be simple and efficiently managed. Type 2 diabetes is a progressive disease and eventually most patients will require insulin at a certain stage to maintain good glycaemic control.
The key to when to start insulin is to identify the appropriate glycated haemoglobin (HbA1c) target for an individual patient. If target A1C is not achieved with metformin combined with sulfonylurea, the most commonly used 2nd line oral hypoglycaemic agents, insulin therapy is usually started. In patients on sulfonylureas and metformin who are starting insulin therapy, metformin is usually continued. Part of the rationale for combination oral hypoglycaemic agents and insulin therapy is that by suppressing hepatic glucose production, the patient can retain the convenience of oral agents while minimizing total insulin requirements and, therefore, the degree of hyperinsulinemia. GLP-1 agonists, DPP-4 inhibitors, and sodium-glucose co-transporter 2 (SGLT2) inhibitors can also be continued when insulin is added, however, they are currently not PBS listed for being combined with insulin. There are no clear guidelines as to whether and at what time point SU are to be discontinued or continued when insulin is introduced. Data from the UKPDS and meta-analyses of several randomized placebo-controlled trials report modest but consistent benefits of a combination of sulfonylurea and metformin with insulin therapy compared with insulin monotherapy. However, the combination of sulfonylurea and insulin is less efficacious and results in more weight gain than metformin and insulin. Furthermore, insulin and sulfonylureas have similar effects of increasing circulating insulin levels, and the same glucose-lowering effect can usually be achieved, and at a lower cost and better prediction, with a modestly higher dose of insulin alone. Furthermore, a recent retrospective Danish study has found that patients with a combination with SU and insulin had an increased mortality compared to metformin and insulin. Studies also report increased risks of weight gain and hypoglycaemia when left on SU while starting basal or pre-mixed insulins.
Based on this recent literature review, it is a concern that many patients with Type 2 Diabetes are continuing their SU together with their pre-mix insulin, with limited evidence for an added benefit, but a growing evidence of increased risk of hypoglycaemia, weight gain and possibly increased mortality. The outcome of this study will give as important information which could lead to a change in current practice guidelines.
The aim of our study is to assess whether SU should be stopped, continued or replaced with a DPP4 Inhibitor once pre-mixed insulin therapy has been started.
We hypothesise that SU will not have a significant additive effect on glycaemic control in patients on pre-mix insulin, but contribute significantly to increased risk of hypoglycaemia and weight gain. A similar glycaemic control can be achieved by a dose adjustment of the insulin dose, or by adding a DPP-IV inhibitor without the side effects of SU, such as hypoglycaemia and weight gain.
Results of this study could have an important impact on how type 2 diabetes patients are treated safely and effectively.

PRIMARY OUTCOMES:
To measure the change in glycaemic control when stopping SU or replacing SU with a DPP-4 inhibitor in patients on pre-mix insulin.
SECONDARY OUTCOMES
To compare the side effects (weight gain) and safety (hypoglycaemia) of stopping SU or replacing SU with a DPP-4 inhibitor in patients with pre-mix insulin.
This is a prospective, randomised, open label controlled single centre trial with three arms:
a) Patients continue SU
b) Patients stop SU
c) Patients replace SU with the DPP4 inhibitor Linagliptin (5mg/day)

Patient characteristics: Patients with Type 2 Diabetes treated with pre-mix insulin (NovoMix30 or HumalogMix25), at least twice daily for at least 6 months, and also treated with SU since at least 4 years. 99 patients in total (33 patients per arm) will be recruited at St Vincent’s Hospital, Sydney.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58586 0
A/Prof Alexander Viardot
Address 58586 0
Diabetes Service, Department of Endocrinology
St Vincent's Hospital
Level 4, Garvan Institute of Medical Research
384 Victoria Street
Darlinghurst NSW 2010
Country 58586 0
Australia
Phone 58586 0
+61 2 8382 2622
Fax 58586 0
Email 58586 0
a.viardot@garvan.org.au
Contact person for public queries
Name 58587 0
A/Prof Alexander Viardot
Address 58587 0
Diabetes Service, Department of Endocrinology
St Vincent's Hospital
Level 4, Garvan Institute of Medical Research
384 Victoria Street
Darlinghurst NSW 2010
Country 58587 0
Australia
Phone 58587 0
+61 2 8382 2622
Fax 58587 0
Email 58587 0
a.viardot@garvan.org.au
Contact person for scientific queries
Name 58588 0
A/Prof Alexander Viardot
Address 58588 0
Diabetes Service, Department of Endocrinology
St Vincent's Hospital
Level 4, Garvan Institute of Medical Research
384 Victoria Street
Darlinghurst NSW 2010
Country 58588 0
Australia
Phone 58588 0
+61 2 8382 2622
Fax 58588 0
Email 58588 0
a.viardot@garvan.org.au

No information has been provided regarding IPD availability
Summary results
No Results