DAPA-HD: SGLT2 Inhibition in Hemodialysis

Sponsor

Medical University of Vienna (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05179668

Collaborator

Vienna Dialysis Center (Other)

108

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Failure Hemodialysis Diabetes Mellitus, Type 2 Chronic Kidney Disease Left Ventricular Hypertrophy	Drug: Dapagliflozin 10 MG Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Aug 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention arm Hemodialysis patients receiving dapagliflozin 10 mg once daily	Drug: Dapagliflozin 10 MG administered orally once daily Other Names: Forxiga 10 MG
Placebo Comparator: Placebo Hemodialysis patients receiving placebo oral tablet once daily	Drug: Placebo administered orally once daily

Arm

Intervention/Treatment

Experimental: Intervention arm

Hemodialysis patients receiving dapagliflozin 10 mg once daily

Drug: Dapagliflozin 10 MG

administered orally once daily

Other Names:

Forxiga 10 MG

Placebo Comparator: Placebo

Hemodialysis patients receiving placebo oral tablet once daily

Drug: Placebo

administered orally once daily

Outcome Measures

Primary Outcome Measures

Δ Left ventricular mass indexed to body surface area [From baseline to 6 months]
measured by cMRI

Secondary Outcome Measures

Δ HbA1c [%] [From baseline to 6 months]
Change in relative %
Δ Left ventricular mass indexed to body height [From baseline to 6 months]
measured by cMRI
Δ Left ventricular ejection fraction [From baseline to 6 months]
measured by cMRI
Δ Cardiac fibrosis [From baseline to 6 months]
measured by cMRI
Δ Body weight [kg] [From baseline to 6 months]
Change in kg

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
High grade heart valve defects
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