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Trial registered on ANZCTR


Registration number
ACTRN12621000152820
Ethics application status
Approved
Date submitted
14/01/2021
Date registered
15/02/2021
Date last updated
15/02/2021
Date data sharing statement initially provided
15/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Empagliflozin and salt restriction in people with type 2 diabetes and chronic kidney disease
Scientific title
A randomised crossover study examining the effects of sodium restriction on 24-hour ambulatory blood pressure in people with type 2 diabetes and chronic kidney disease treated with empagliflozin
Secondary ID [1] 303146 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 320257 0
Chronic kidney disease 320258 0
Condition category
Condition code
Metabolic and Endocrine 318188 318188 0 0
Diabetes
Renal and Urogenital 318189 318189 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Empagliflozin 10 mg once daily oral tablet for 4 weeks combined with sodium restriction for 4 weeks.
Participants will be randomised to start with empagliflozin combined with sodium restriction for 4 weeks or empagliflozin combined with their usual sodium intake for 4 weeks. Participants will then undergo a 2-week washout period and crossover to the alternative sodium intervention (usual sodium intake or sodium restriction) combined with empagliflozin for 4 weeks.
Adherence to taking empagliflozin will be monitored with the use of a participant study diary to record the administration of each empagliflozin tablet.
A Dietician with minimum 3 years experience will provide education to participants individually regarding sodium restriction over the internet or via telephone call. Participants can receive this virtual education at their homes. The Dietician will provide an initial education session (approximately 1-2 hours) at the time of randomisation to sodium restriction (in the week prior to starting empagliflozin treatment) and then have a follow-up session (approximately 30 minutes - 1 hour) 1-2 weeks after the initial individual education and after starting empagliflozin treatment. Information provided to participants at the initial education session will include discussion of foods high in sodium and how to substitute high sodium foods for foods lower in sodium during the sodium restriction period. At the follow-up session the Dietician will discuss the participant's progress with a sodium-restricted diet. The participant will be asked to follow a sodium-restricted diet for 4 weeks. Changes to sodium intake will be monitored with a participant food diary.
Intervention code [1] 319449 0
Treatment: Drugs
Intervention code [2] 319450 0
Lifestyle
Comparator / control treatment
Empagliflozin 10 mg once daily oral tablet for 4 weeks combined with liberal sodium intake for 4 weeks.
Participants will be informed to continue with their usual diet during this 4 week period.
Note this is a crossover study.
Control group
Active

Outcomes
Primary outcome [1] 326174 0
Change in 24-hour ambulatory blood pressure using a 24-hour ambulatory blood pressure device
Timepoint [1] 326174 0
Baseline, 4 weeks after intervention commencement
Secondary outcome [1] 390374 0
Change in urine albumin-to-creatinine ratio (24-hour collection)
Timepoint [1] 390374 0
Baseline, 4 weeks after intervention commencement
Secondary outcome [2] 390375 0
Empagliflozin concentration in plasma
Timepoint [2] 390375 0
Baseline, 4 weeks after intervention commencement
Secondary outcome [3] 390376 0
Change in estimated glomerular filtration rate (eGFR) measured using a peripheral blood sample
Timepoint [3] 390376 0
Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation
Secondary outcome [4] 390377 0
Change in serum creatinine
Timepoint [4] 390377 0
Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation
Secondary outcome [5] 390378 0
Change in haematocrit measured using a peripheral blood sample
Timepoint [5] 390378 0
Baseline, 2 weeks and 4 weeks after intervention commencement, 2 weeks after intervention cessation
Secondary outcome [6] 390379 0
Change in serum uric acid
Timepoint [6] 390379 0
Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation
Secondary outcome [7] 390380 0
Change in serum phosphate
Timepoint [7] 390380 0
Baseline, 4 weeks after intervention commencement, 2 weeks after intervention cessation
Secondary outcome [8] 390381 0
Change in serum fructosamine
Timepoint [8] 390381 0
Baseline, 4 weeks after intervention commencement
Secondary outcome [9] 390382 0
Change in serum fasting beta-hydroxybutyrate measured using a peripheral blood sample
Timepoint [9] 390382 0
Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation
Secondary outcome [10] 390383 0
Change in fractitional endogenous lithium excretion - measured using a peripheral blood and urine sample
Timepoint [10] 390383 0
Baseline, 4 weeks after intervention commencement
Secondary outcome [11] 390384 0
Change in total body water estimated by bioimpedance spectroscopy (measured using ImpediMed SFB7 device)
Timepoint [11] 390384 0
Baseline, 4 weeks after intervention commencement
Secondary outcome [12] 390385 0
Change in extracellular fluid volume estimated by bioimpedance spectroscopy (measured using ImpediMed SFB7 device)
Timepoint [12] 390385 0
Baseline, 4 weeks after intervention commencement
Secondary outcome [13] 390386 0
Change in intracellular fluid volume estimated by bioimpedance spectroscopy (measured using ImpediMed SFB7 device)
Timepoint [13] 390386 0
Baseline, 4 weeks after intervention commencement

Eligibility
Key inclusion criteria
- Age range: 18 - 75 years
- Diagnosis of type 2 diabetes and HbA1c up to 10%
- Stage 2, 3 or 4 CKD (eGFR 60-89 mL/min/1.73 m2 and urine albumin-to-creatinine ratio >30 mg/g, eGFR 30-59 mL/min/1.73m2 or 15 – 29 mL/min/1.73m2, respectively) at the time of screening, and stable renal function defined as a difference of <30% between two consecutive eGFR in the 3 months before the screening visit
- On stable anti-hypertensive dose of an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) in the one month before the screening visit
- Willing to give written informed consent and willingness to participate to and comply with the study
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Symptomatic hypotension, systolic blood pressure less than 110 mmHg or hypertension – systolic blood pressure greater than 170 mmHg
- Liver disease (alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) greater than 3-times normal range limit)
- On haemodialysis or peritoneal dialysis
- Serum potassium of greater than or equal to 6.0 mmol/L
- Type 1 diabetes, diabetes secondary to pancreatic disease, history of diabetic ketoacidosis
- History of neoplastic disease (except for basal cell carcinoma) in the previous 1 year.
- History of recurrent urinary tract infections, genital infections and/or urogenital structural abnormalities
- Overt nephrotic syndrome
- Acute coronary syndrome, stroke, transient ischaemic attack, or other cardiovascular event within 3 months of screening
- Use of the following medications: current treatment with a SGLT2 inhibitor, current or recent (within 3 months) treatment with a glucagon-like peptide-1 (GLP1) agonist, treatment with a glucocorticoid, treatment with a non-steroidal anti-inflammatory drug (at least weekly), investigational new drug within the last 3 months
- Previous bariatric surgery
- Uncontrolled endocrine disorder except type 2 diabetes mellitus
- Current smoker
- Alcohol intake greater than or equal to 14 standard drinks per week
- Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study
- History of a psychological illness or condition such as to interfere with a person’s ability to understand the requirements of the study.

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 to start with sodium restriction or liberal sodium intake will occur with simple randomisation using a randomisation table created by computer software.
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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/02/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 18391 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 32481 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 307548 0
Charities/Societies/Foundations
Name [1] 307548 0
St Vincent's Clinic Foundation
Country [1] 307548 0
Australia
Funding source category [2] 307551 0
Charities/Societies/Foundations
Name [2] 307551 0
Heart Foundation
Country [2] 307551 0
Australia
Funding source category [3] 307552 0
University
Name [3] 307552 0
St Vincent's Clinical School
Country [3] 307552 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
390 Victoria Street Darlinghurst New South Wales 2010
Country
Australia
Secondary sponsor category [1] 308259 0
None
Name [1] 308259 0
Address [1] 308259 0
Country [1] 308259 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307614 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 307614 0
Ethics committee country [1] 307614 0
Australia
Date submitted for ethics approval [1] 307614 0
Approval date [1] 307614 0
19/09/2018
Ethics approval number [1] 307614 0
2019/ETH033034

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

Contacts
Principal investigator
Name 107870 0
Prof Richard Day
Address 107870 0
Department of Clinical Pharmacology and Toxicology, Level 2 Xavier Building, St Vincent's Hospital, 390 Victoria St Darlinghurst NSW 2010
Country 107870 0
Australia
Phone 107870 0
+61 283822304
Fax 107870 0
Email 107870 0
[email protected]
Contact person for public queries
Name 107871 0
Tamara Milder
Address 107871 0
Department of Clinical Pharmacology and Toxicology, Level 2 Xavier Building, St Vincent's Hospital, 390 Victoria St Darlinghurst NSW 2010
Country 107871 0
Australia
Phone 107871 0
+61 283822304
Fax 107871 0
Email 107871 0
[email protected]
Contact person for scientific queries
Name 107872 0
Tamara Milder
Address 107872 0
Department of Clinical Pharmacology and Toxicology, Level 2 Xavier Building, St Vincent's Hospital, 390 Victoria St Darlinghurst NSW 2010
Country 107872 0
Australia
Phone 107872 0
+61 283822304
Fax 107872 0
Email 107872 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


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.