Ignite Creation Date:
2024-05-06 @ 9:47 AM
Last Modification Date:
2024-10-26 @ 12:20 PM
Study NCT ID:
NCT03078101
Status:
COMPLETED
Last Update Posted:
2019-08-08
First Post:
2017-03-07
Brief Title:
EMPRA EMPagliflozin and RAs in Kidney Disease
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
Effect of Empagliflozin on the Renin-angiotensin System in Patients With Chronic
Status:
COMPLETED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EMPRA
Brief Summary:
This study will be a prospective clinical pilot study in CKD patients to show whether Empagliflozin in addition to ACEi treatment significantly increases Ang 1-7 levels compared to ACEi treatment alone
Null and alternative hypotheses
H0 Empagliflozin in addition to ACEi treatment does not increase Ang 1-7 levels more than ACEi treatment alone
H1 Empagliflozin in addition to ACEi treatment significantly increases Ang 1-7 levels compared to ACEi treatment alone
Methodology
Two groups of 24 chronic kidney disease CKD patients respectively with and without type 2 diabetes will be randomized into the study medication or placebo group The number of patients per treatment arms is n 12 Included and consented patients will be subjected to an initial 2-week run-in period for conversion of current RAS blocking medications to ACEi therapy with enalapril or ramipril and respective dose titration to 10 mg enalapril 2 x daily and 10 mg ramipril 1 x daily Additional antihypertensive medication will be standardized as feasible with the primary goal of keeping blood pressure as recommended by KDIGO Following the 2-week run-in phase all study patients will be subjected to blood collection including the first RAS quantification RAS Fingerprint and assessment of HDL composition as well as urinary analysis and bioimpedance fluid status assessment BCM measurement Subsequently patients will be randomized to either receive empagliflozin at a dose of 10 mg daily or placebo Subsequently biweekly study visits including electrolyte and glucose plasma and urine monitoring as well as BCM measurement will take place After 12 weeks of study medication intake a concluding study visit will be scheduled for final RAS quantification RAS Fingerprint and HDL analyses as well as final blood and urinary analysis and BCM measurement Initially blood and urine will be collected at the clinical visit as part of the routine blood obtainment no additional effort on patients From these routine measurements we will be able to extract information regarding the patients current CKD stage as well as other relevant laboratory parameters eg HbA1c UACR etc Furthermore we will document the patients current medication and significant comorbidities
Primary analysis variableendpoint
The difference of Ang 1-7 increase from baseline between a 3-month treatment with empagliflozin on top of ACEi treatment compared to ACEi treatment alone
Most important secondary analysis variablesendpoints
1 Simultaneous quantitative changes of multiple RAS effector angiotensin levels determined by mass-spectrometry
2 Recurrence of Ang II levels determined by mass-spectrometry
3 HDL parameters protein composition of HDL
4 Renal parameters albuminuria reduction measured by urinary albumin-creatinine ratio UACR renal function estimated glomerular filtration rate GFR serum-creatinine
5 Urinary electrolyte levels
6 Urinary glucose levels
7 Urinary RAS metabolites angiotensinogen ACE and ACE2 levels ACE2 activity
8 Blood pressure determined by ambulatory blood pressure measurements
9 Body volume determined by bioimpedance fluid status assessment BCM measurement
10 OCR and ECAR in PBMCs determined by Seahorse Flux Analyzer
11 Assessment of reduction of salt sensitivity by using salt sensitivity test with empagliflozin
Null and alternative hypotheses
H0 Empagliflozin in addition to ACEi treatment does not increase Ang 1-7 levels more than ACEi treatment alone
H1 Empagliflozin in addition to ACEi treatment significantly increases Ang 1-7 levels compared to ACEi treatment alone
Methodology
Two groups of 24 chronic kidney disease CKD patients respectively with and without type 2 diabetes will be randomized into the study medication or placebo group The number of patients per treatment arms is n 12 Included and consented patients will be subjected to an initial 2-week run-in period for conversion of current RAS blocking medications to ACEi therapy with enalapril or ramipril and respective dose titration to 10 mg enalapril 2 x daily and 10 mg ramipril 1 x daily Additional antihypertensive medication will be standardized as feasible with the primary goal of keeping blood pressure as recommended by KDIGO Following the 2-week run-in phase all study patients will be subjected to blood collection including the first RAS quantification RAS Fingerprint and assessment of HDL composition as well as urinary analysis and bioimpedance fluid status assessment BCM measurement Subsequently patients will be randomized to either receive empagliflozin at a dose of 10 mg daily or placebo Subsequently biweekly study visits including electrolyte and glucose plasma and urine monitoring as well as BCM measurement will take place After 12 weeks of study medication intake a concluding study visit will be scheduled for final RAS quantification RAS Fingerprint and HDL analyses as well as final blood and urinary analysis and BCM measurement Initially blood and urine will be collected at the clinical visit as part of the routine blood obtainment no additional effort on patients From these routine measurements we will be able to extract information regarding the patients current CKD stage as well as other relevant laboratory parameters eg HbA1c UACR etc Furthermore we will document the patients current medication and significant comorbidities
Primary analysis variableendpoint
The difference of Ang 1-7 increase from baseline between a 3-month treatment with empagliflozin on top of ACEi treatment compared to ACEi treatment alone
Most important secondary analysis variablesendpoints
1 Simultaneous quantitative changes of multiple RAS effector angiotensin levels determined by mass-spectrometry
2 Recurrence of Ang II levels determined by mass-spectrometry
3 HDL parameters protein composition of HDL
4 Renal parameters albuminuria reduction measured by urinary albumin-creatinine ratio UACR renal function estimated glomerular filtration rate GFR serum-creatinine
5 Urinary electrolyte levels
6 Urinary glucose levels
7 Urinary RAS metabolites angiotensinogen ACE and ACE2 levels ACE2 activity
8 Blood pressure determined by ambulatory blood pressure measurements
9 Body volume determined by bioimpedance fluid status assessment BCM measurement
10 OCR and ECAR in PBMCs determined by Seahorse Flux Analyzer
11 Assessment of reduction of salt sensitivity by using salt sensitivity test with empagliflozin
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None