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Trial registered on ANZCTR


Registration number
ACTRN12618001907235
Ethics application status
Approved
Date submitted
21/11/2018
Date registered
23/11/2018
Date last updated
23/07/2019
Date data sharing statement initially provided
23/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
WORTH (which one is right here?): Randomised, crossover study to identify predictive baseline characteristics of response to pioglitazone or vildagliptin as second or third line therapy in patients with Type 2 diabetes
Scientific title
WORTH (which one is right here?): Randomised, crossover study to identify predictive baseline characteristics of response to pioglitazone or vildagliptin as second or third line therapy in patients with Type 2 diabetes
Secondary ID [1] 296667 0
Nil known
Universal Trial Number (UTN)
U1111-1224-3141
Trial acronym
WORTH study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 310510 0
Condition category
Condition code
Metabolic and Endocrine 309224 309224 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Crossover study of two medications:
Vildagliptin 50mg oral tablet, once daily for 4 months
Pioglitazone 30mg oral tablet, once daily for 4 months
In random order without any washout period.
Adherence monitored by bottle returns and participant recall.
Intervention code [1] 312979 0
Treatment: Drugs
Comparator / control treatment
Crossover study of two medications:
Vildagliptin 50mg oral tablet, once daily for 4 months
Pioglitazone 30mg oral tablet, once daily for 4 months
In random order without any washout period.
Adherence monitored by bottle returns and participant recall.
Control group
Active

Outcomes
Primary outcome [1] 308187 0
HbA1c
Timepoint [1] 308187 0
end of 4 months drug treatment
Secondary outcome [1] 354201 0
Patient preference using Diabetes Treatment Satisfaction Questionnaire standard and change versions i.e: DTSQs and DTSQc (latter only administered at the conclusion of the study).
Timepoint [1] 354201 0
end of 8 months of drug treatment

Eligibility
Key inclusion criteria
• Clinical diagnosis of Type 2 diabetes
• Diabetes duration greater than or equal to 12 months
• Age between 18 and 80 years inclusive
• Currently treated with metformin and/or sulphonylureas and no past or current treatment with a DPP4-inhibitor or a thiazolidinedione.
• No treatment with insulin in the last 3 months
• Diabetes duration greater than or equal to 12months
• No change in diabetes treatment (new treatments or dose change) within previous 3 months
• HbA1c greater than 58mmol/mol (7.5%) and less than or equal to 110mmol/mol (12.2%) – confirmed at screening
• Able and willing to give informed consent
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Changes in glucose-lowering therapy or dose within last 3 months
• Insulin treated within the last 3 months
• Treatment with study drugs in the past
• Currently treated with oral corticosteroids
• Currently treated with rifampicin, gemfibrozil, phenytoin or carbamazepine
• Active infection (any infection requiring antibiotics at present)
• Active liver disease (AST or ALT over 3 times upper limit of normal)
• Heart failure greater than NYHA class 2
• History of bladder carcinoma
• Current/ongoing investigation for macroscopic haematuria
• History of Diabetic Ketoacidosis
• History of pancreatitis
• Pregnant, breastfeeding or planning a pregnancy over the study period
• Concurrent Participation on another Clinical Trial of an Investigational Medicinal Product, where the IMP is currently being taken, or without sufficient washout period* and without consultation with the CTIMP research team.
• Unable or unwilling to give informed consent
* Sufficient washout period equals five times the half-life of the IMP / potential IMP if involving a placebo / longest half-life if a trial includes more than one drug.

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 not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation lists for each site will be computer generated and stored in a secure study database for online randomisation across all sites. Block randomisation with variable block sizes will be used to generate the randomisation sequences (AB vs BA) stratified by district health board catchment region of recruitment and ethnicity (Maori/Pacific vs non-Maori/non-Pacific).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This is not a standard crossover study of comparative drug efficacy, but a study examining whether there is stratification in drug response (HbA1c change) by key baseline characteristics such as ethnicity, genotype, and BMI. The primary outcome variable is on treatment HbA1c after 4 months on each of the two drugs. The key primary analysis for each hypothesis is to assess whether the difference in achieved HbA1c for the two drugs is different by ethnicity grouping of patients. Generalised linear mixed model will be used to test the difference between patient groups using both fixed and random effects. The fixed effects will include the baseline outcome value, stratification factors, crossover period, drug class, patient group and its interaction with drug. The random effect will include patient as the cluster. Statistical analysis will be performed based on the intention-to-treat principle.

Recruitment
Recruitment status
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 outside Australia
Country [1] 21056 0
New Zealand
State/province [1] 21056 0

Funding & Sponsors
Funding source category [1] 301246 0
Government body
Name [1] 301246 0
Health Research Council of New Zealand
Address [1] 301246 0
PO Box 5541
Wellesley St
Auckland 1141
Country [1] 301246 0
New Zealand
Funding source category [2] 301248 0
Charities/Societies/Foundations
Name [2] 301248 0
Middlemore Clinical Trials Trust
Address [2] 301248 0
Private Bag 93311
Auckland 1640
Country [2] 301248 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 300904 0
None
Name [1] 300904 0
Address [1] 300904 0
Country [1] 300904 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301985 0
Northern A Health and disability ethics committee
Ethics committee address [1] 301985 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 301985 0
New Zealand
Date submitted for ethics approval [1] 301985 0
21/11/2018
Approval date [1] 301985 0
12/02/2019
Ethics approval number [1] 301985 0

Summary
Brief summary
This is a two-period (4 months each), two-treatment, randomised crossover study of a DPP4 inhibitor (vildagliptin), and thiazolidinedione (pioglitazone) as second or third line oral therapy in patients with type 2 diabetes who have suboptimal glycaemic control on therapy with either metformin alone, or metformin and a sulphonylurea. The study aims to determine whether baseline characteristics such as ethnicity, genotype, obesity, lipids impacts on the glucose lowering response achieved by either of these two oral medications used to treat Type 2 diabetes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88766 0
A/Prof Rinki Murphy
Address 88766 0
University of Auckland,
Department of Medicine
Faculty of medical and health sciences
Private Bag 92019
Auckland 1142
Country 88766 0
New Zealand
Phone 88766 0
+64 9 9236313
Fax 88766 0
Email 88766 0
R.Murphy@auckland.ac.nz
Contact person for public queries
Name 88767 0
A/Prof Rinki Murphy
Address 88767 0
University of Auckland,
Department of Medicine
Faculty of medical and health sciences
Private Bag 92019
Auckland 1142
Country 88767 0
New Zealand
Phone 88767 0
+64 9 9236313
Fax 88767 0
Email 88767 0
R.Murphy@auckland.ac.nz
Contact person for scientific queries
Name 88768 0
A/Prof Rinki Murphy
Address 88768 0
University of Auckland,
Department of Medicine
Faculty of medical and health sciences
Private Bag 92019
Auckland 1142
Country 88768 0
New Zealand
Phone 88768 0
+64 9 9236313
Fax 88768 0
Email 88768 0
R.Murphy@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The genotype and medical information collected as part of this study requires consultation with our Maori and Pacific research partners as to whether individual participant data for this trial will be made available on public repositories. This is to safeguard from possible misuse of the data to investigate ideas that were not consented for by the participants for research.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 3367 0
Study protocol
Citation [1] 3367 0
Link [1] 3367 0
Email [1] 3367 0
Other [1] 3367 0
Type [2] 3368 0
Informed consent form
Citation [2] 3368 0
Link [2] 3368 0
Email [2] 3368 0
Other [2] 3368 0
Type [3] 3369 0
Ethical approval
Citation [3] 3369 0
Link [3] 3369 0
Email [3] 3369 0
Other [3] 3369 0
Summary results
No Results