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Trial registered on ANZCTR


Registration number
ACTRN12616001535460
Ethics application status
Approved
Date submitted
3/10/2016
Date registered
8/11/2016
Date last updated
9/11/2018
Date data sharing statement initially provided
9/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Cardiac Magnetic Resonance (MR) changes with empagliflozin treatment in people with type 2 diabetes: a pilot study
Scientific title
Cardiac MR changes with empagliflozin treatment in people with type 2 diabetes: a pilot study
Secondary ID [1] 290260 0
2016-02-131
Baker IDI Heart and Diabetes Institute ID number
Universal Trial Number (UTN)
U1111-1188-2435
Trial acronym
Linked study record
no linked study

Health condition
Health condition(s) or problem(s) studied:
type 2 diabetes 300480 0
heart failure 300481 0
cardiovascular disease 300482 0
Condition category
Condition code
Metabolic and Endocrine 300336 300336 0 0
Diabetes
Cardiovascular 300337 300337 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. EXPOSURE
allocation: empagliflozin as per clinical indication
dose: 10 mg daily
mode of administration: oral tablet
duration: 6 months minimum and ongoing unless clinical indication to cease

2. INVESTIGATIONS
(i) height and weight which takes 2 minutes
(ii) blood test for HbA1c and BNP which takes 2 minutes
(iii) New York Heart Association Functional Classification questionnaire which takes 1 minutes
(iv) cardiac MRI which takes 90 minutes

3. DURATION OF FOLLOW-UP
6 months
all investigations are undertaken at baseline and at 6 months follow-up
Intervention code [1] 296200 0
Diagnosis / Prognosis
Comparator / control treatment
COMPARATOR
standard care in relation to glycemic control WITHOUT SGLT2 inhibitor therapy
this group will also under go cardiac MR and blood tests at baseline and at 6 months follow-up
Control group
Active

Outcomes
Primary outcome [1] 299802 0
cardiac MR - LV-EDV index/LV ejection fraction/LV mass
Timepoint [1] 299802 0
baseline and 6 months
Primary outcome [2] 299950 0
cardiac MR - native (non-contrast) T1 mapping for assessment of diffuse myocardial fibrosis / T2* for assessment of myocardial iron load
Timepoint [2] 299950 0
baseline and 6 months
Secondary outcome [1] 328170 0
BNP (brain or b-type naturetic peptide) - serum assay
Timepoint [1] 328170 0
baseline and 6 months
Secondary outcome [2] 328171 0
New York Heart Association Functional Classification - questionnaire
Timepoint [2] 328171 0
baseline and 6 months
Secondary outcome [3] 328635 0
weight - clinical examination
Timepoint [3] 328635 0
baseline and 6 months
Secondary outcome [4] 328636 0
blood pressure - clinical examination
Timepoint [4] 328636 0
baseline and 6 months
Secondary outcome [5] 328637 0
glycemic control by HbA1c - serum assay
Timepoint [5] 328637 0
baseline and 6 months
Secondary outcome [6] 328638 0
medication or medication changes - clinical review
Timepoint [6] 328638 0
baseline and 6 months

Eligibility
Key inclusion criteria
Sex: all

Age: 18 - 75 years

Disease status and severity: type 2 diabetes with HbA1c > 7% (in accordance with PBS requirements)

Informed consent: participant must be able to give personal informed consent
Participation in the study: participant must be able to co-operate sufficiently to allow the proposed study to progress.

Concomitant medications: no restriction is made in the use of concomitant medications, which will be left to the treating specialist
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age: less than 18 years and greater than 75 years

Disease status and severity: type 1 diabetes and type 2 diabetes with HbA1c less than 7%

Pregnancy and breast feeding: females must not be pregnant or breast feeding or at risk of becoming pregnant (permanent or effective contraception required – hysterectomy, tubal ligation, IUD or OCP)

Concomitant medications: No restriction in concomitant medications except the use of an SGLT2 inhibitor the control group.

Contraindications to magnetic resonance imaging: metallic implants

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
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Calculation of sample size is limited by the lack of information on expected changes seen with SGLT2 treatment. Published algorithm by Pitcher at al suggests that for parallel study designs with before and after treatment cardiac magnetic resonance imaging scans appropriate sample sizes are 10-15 per treatment group for LV-ejection fraction and LV mass (power 80%, P-value 0.05). A 25% drop out rate has been incorporated in the sample size resulting in the final sample size of 20 participants in each group (total 40 participants).
Statistical methods used to examine differences between empagliflozin treatment status (categorical – YES or NO) and:
(i) baseline cardiac magnetic resonance imaging parameters, BNP and heart failure questionnaire score (all continuous variables) will be by unpaired t-test. This will indicate any evidence of pre-existing differences between the two treatment groups which will need to be considered as possible confounding or bias in the final analysis and report.
(ii) effect of confounding clinical factors of age, weight, blood pressure and glycemic control on baseline cardiac magnetic resonance imaging parameters, BNP and heart failure questionnaire score (all continuous variables) will be by ANCOVA. The impact of these clinical factors on the primary and secondary outcomes of the study is important for the formulation of future cardiac magnetic resonance imaging studies in studies of people with type 2 diabetes as well as in the interpretation of these findings in this study, particularly if pre-existing differences between the two treatment groups is identified in (i).
(iii) change in cardiac magnetic resonance imaging parameters, BNP and heart failure questionnaire score (all continuous variables) will be by repeated ANOVA

Exploratory examination of effects of disease duration, age, renal function, weight, blood pressure, glycemic control and medication on cardiac magnetic resonance imaging parameters (all continuous variables) will be undertaken by Pearson r correlation for normally distributed data and by Spearman rank correlation for non-normally distributed data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
16/05/2016
Date of last participant enrolment
Anticipated
1/11/2017
Actual
16/05/2017
Date of last data collection
Anticipated
1/05/2018
Actual
31/10/2017
Sample size
Target
40
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 294629 0
Other
Name [1] 294629 0
Baker IDI Heart and Diabetes Institute
Country [1] 294629 0
Australia
Primary sponsor type
Other
Name
Baker IDI Heart and Diabetes Institute
Address
75 Commercial Road, Melbourne Victoria 3004
Country
Australia
Secondary sponsor category [1] 293493 0
None
Name [1] 293493 0
Address [1] 293493 0
Country [1] 293493 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296069 0
Bellberry
Ethics committee address [1] 296069 0
Ethics committee country [1] 296069 0
Australia
Date submitted for ethics approval [1] 296069 0
21/03/2016
Approval date [1] 296069 0
16/05/2016
Ethics approval number [1] 296069 0
no Approval ID provided

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

Contacts
Principal investigator
Name 69426 0
A/Prof Neale Cohen
Address 69426 0
Baker IDI, Level 4, 99 Commercial Road, Melbourne, Victoria 3004
Country 69426 0
Australia
Phone 69426 0
+61 3 8532 1816
Fax 69426 0
Email 69426 0
[email protected]
Contact person for public queries
Name 69427 0
Erin Boyle
Address 69427 0
Baker IDI, Level 4, 99 Commercial Road, Melbourne, Victoria 3004
Country 69427 0
Australia
Phone 69427 0
+61 3 8532 1828
Fax 69427 0
Email 69427 0
[email protected]
Contact person for scientific queries
Name 69428 0
Esther Briganti
Address 69428 0
Baker IDI, Level 4, 99 Commercial Road, Melbourne, Victoria 3004
Country 69428 0
Australia
Phone 69428 0
+61 3 8532 1838
Fax 69428 0
+61 3 8532 1899
Email 69428 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
NA


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.