SGLT2 Inhibition in Hemodialysis (DAPA-HD)
Primary Purpose
Kidney Failure, Hemodialysis, Diabetes Mellitus, Type 2
Status
Recruiting
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
Dapagliflozin 10 MG
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Failure focused on measuring Dapagliflozin, SGLT2 inhibition
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years
- Maintenance hemodialysis 3×/week for ≥3 months and ≤3 years
- BMI <45 kg/m2 and stable weight (± 5 kg ["dry weight"]) over the preceding three months
- Signed informed consent
Exclusion Criteria:
Study specific:
- Contraindications for MRI
- Hypersensitivity or Intolerance of SGLT2 inhibitors
- Participation in another clinical trial
Medical condition specific:
- History of diabetic ketoacidosis
- Interventricular septum width ≤ 11 mm
- Severe valvular heart disease
- Life expectancy < 1 year
- Substance abuse
- History of Type 1 diabetes mellitus
- Scheduled kidney transplant from a living donor
- Other significant disease or pathology, that might predispose that patient to an unacceptable risk or interferes with the study in the opinion of the investigator.
- Acute coronary syndrome during the last 30 days
- Existing treatments with SGLT2i within the last 6 months
Female specific:
- Child bearing potential & unwilling / unable to use an acceptable method to avoid pregnancy for the entire study (estrogen and/or progesterone treatment).
- Pregnancy
- Breast feeding
Sites / Locations
- Medical University of ViennaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Intervention arm
Placebo
Arm Description
Hemodialysis patients receiving dapagliflozin 10 mg once daily
Hemodialysis patients receiving placebo oral tablet once daily
Outcomes
Primary Outcome Measures
Δ Left ventricular mass indexed to body surface area
measured by cMRI
Secondary Outcome Measures
Δ HbA1c [%]
Change in relative %
Δ Left ventricular mass indexed to body height
measured by cMRI
Δ Left ventricular ejection fraction
measured by cMRI
Δ Cardiac fibrosis
measured by cMRI
Δ Body weight [kg]
Change in kg
Full Information
NCT ID
NCT05179668
First Posted
December 16, 2021
Last Updated
October 21, 2022
Sponsor
Medical University of Vienna
Collaborators
Vienna Dialysis Center
1. Study Identification
Unique Protocol Identification Number
NCT05179668
Brief Title
SGLT2 Inhibition in Hemodialysis
Acronym
DAPA-HD
Official Title
SGLT2 Inhibition (Dapagliflozin) in Diabetic and Non-diabetic Hemodialysis Patients With and Without Residual Urine Volume: a Prospective Randomized, Placebo-controlled, Double-blinded Phase II Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
April 1, 2025 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
Collaborators
Vienna Dialysis Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study is designed as a prospective randomized, controlled, double-blinded phase II trial to examine the effect of the SGLT2 inhibitor dapagliflozin, in comparison with placebo on cardiovascular outcome parameters in kidney failure patients undergoing replacement therapy with hemodialysis.
The primary endpoint is the change (∆) in left ventricular mass indexed to body surface area (LVMi) from baseline to 6 months measured by cardiac magnetic resonance imaging.
Null and alternative hypotheses:
H0: There is no difference in the ∆ Left Ventricular Mass indexed to BSA after six months of treatment, comparing patients having received the SGLT2-Inhibitor Dapagliflozin versus placebo.
H1: There is a difference in the ∆ Left Ventricular Mass indexed to BSA comparing patients having received the SGLT2-Inhibitor Dapagliflozin versus placebo.
Detailed Description
The parallel groups will receive dapagliflozin 10 mg vs. placebo (1:1 manner; n = 54 per group) for 6 months. Cardiological outcome parameters will include the change in left ventricular mass (LVM), left ventricular ejection fraction (EF), cardiac fibrosis and left atrial diameter (LAD) from baseline to 6 months measured by cMRI and strain echocardiography.
Biochemical data will be collected prior to hemodialysis at baseline and periodically (e.g. blood gas analysis at every dialysis visit, measurements of and pre- and post- dialysis troponin T (TnT) and pro brain natriuretic peptide (proBNP) every 4 weeks).
A full laboratory analysis of blood cell count, blood coagulation and clinical chemistry will be performed at baseline, 3 months, and 6 months. Additionally, body weight will be measured at all study visits to monitor changes after SGLT2 inhibitor administration. Hospitalizations and mortality will be monitored clinically.
Further secondary endpoints are glucometabolic parameters (HbA1c, plasma values of insulin, c-peptide, glucagon, glucagon-Like peptide-1 (GLP1), cortisol, growth hormone, alanine, β-hydroxybutyrate (βOHB) [=ketone] and pyruvate concentration) and will be determined at baseline, 3 and 6 months. The HOMA-Indices will be calculated with the values of insulin and fasting glucose for monitoring of diabetes performed at baseline, 3 months, and 6 months.
Volume status and fluid composition will be measured by bioimpedance spectroscopy at the baseline, 3 months, and end-of-study-visit. In case of hypervolemia, ultrafiltration parameters will be adapted to reach a dry weight based in synopsis of clinical status and body composition monitoring results.
In terms of urinary output and tubuloglomerular feedback, a stratification by residual urine volume by 200 mL per day will be performed to elucidate study aim IV. Prior results of diabetes independent renal and cardiovascular benefit legitimate an examination of groups with and without prevalent diabetes mellitus.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Failure, Hemodialysis, Diabetes Mellitus, Type 2, Chronic Kidney Disease, Left Ventricular Hypertrophy
Keywords
Dapagliflozin, SGLT2 inhibition
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
108 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention arm
Arm Type
Experimental
Arm Description
Hemodialysis patients receiving dapagliflozin 10 mg once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Hemodialysis patients receiving placebo oral tablet once daily
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10 MG
Other Intervention Name(s)
Forxiga 10 MG
Intervention Description
administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
administered orally once daily
Primary Outcome Measure Information:
Title
Δ Left ventricular mass indexed to body surface area
Description
measured by cMRI
Time Frame
From baseline to 6 months
Secondary Outcome Measure Information:
Title
Δ HbA1c [%]
Description
Change in relative %
Time Frame
From baseline to 6 months
Title
Δ Left ventricular mass indexed to body height
Description
measured by cMRI
Time Frame
From baseline to 6 months
Title
Δ Left ventricular ejection fraction
Description
measured by cMRI
Time Frame
From baseline to 6 months
Title
Δ Cardiac fibrosis
Description
measured by cMRI
Time Frame
From baseline to 6 months
Title
Δ Body weight [kg]
Description
Change in kg
Time Frame
From baseline to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Maintenance hemodialysis 3×/week for ≥3 months and ≤3 years
BMI <45 kg/m2 and stable weight (± 5 kg ["dry weight"]) over the preceding three months
Signed informed consent
Exclusion Criteria:
Study specific:
Contraindications for MRI
Hypersensitivity or Intolerance of SGLT2 inhibitors
Participation in another clinical trial
Medical condition specific:
History of diabetic ketoacidosis
Interventricular septum width ≤ 11 mm
Severe valvular heart disease
Life expectancy < 1 year
Substance abuse
History of Type 1 diabetes mellitus
Scheduled kidney transplant from a living donor
Other significant disease or pathology, that might predispose that patient to an unacceptable risk or interferes with the study in the opinion of the investigator.
Acute coronary syndrome during the last 30 days
Existing treatments with SGLT2i within the last 6 months
Female specific:
Child bearing potential & unwilling / unable to use an acceptable method to avoid pregnancy for the entire study (estrogen and/or progesterone treatment).
Pregnancy
Breast feeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christopher Paschen, MD
Phone
014040043910
Email
christopher.paschen@meduniwien.ac.at
First Name & Middle Initial & Last Name or Official Title & Degree
Manfred Hecking, MD, PhD
Phone
014040043910
Email
manfred.hecking@meduniwien.ac.at
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manfred Hecking, MD, PhD
Organizational Affiliation
Medical University of Vienna, Department of Medicine III, Division of Nephrology and Dialysis
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Paschen
Email
christopher.paschen@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Manfred Hecking
Email
manfred.hecking@meduniwien.ac.at
12. IPD Sharing Statement
Plan to Share IPD
No
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SGLT2 Inhibition in Hemodialysis
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