Dapagliflozin on Volume Vascular Outcomes.
- Registration Number
- NCT04869124
- Lead Sponsor
- Frank Ruschitzka
- Brief Summary
The purpose of the DAPA-VOLVO trial is to investigate the effects of Dapagliflozin on top of recommended standard therapy on volume status and vascular function in clinically stable de novo or chronic heart failure patients after hospitalization because of an acute decompensated heart failure event.
- Detailed Description
Recent clinical trials found that Dapagliflozin can reduce the risk of cardiovascular events, hospitalization and death in heart failure (HF) patients with reduced left ventricular ejection fraction (HFrEF) in the presence of absence of diabetes. Additional trials are ongoing to investigate whether these results can be translated also to HF-patients with preserved ejection fraction (HFpEF). However, the underlying mechanisms leading to the improved clinical outcomes are not completely understood but the beneficial effects of Dapagliflozin on volume status and vascular function are discussed as potential key factors. This study is designed as a mechanistic study to investigate the impact of Dapagliflozin on volume status and vascular function in clinically stable de novo or chronic heart failure patients after hospitalization/ ambulatory care because of an acute decompensated heart failure (ADHF) event. After being informed about the study and potential risks all patients given written informed consent will be screened for the defined eligibility criteria and thereafter randomized in a double-blind manner (patients, investigators) 1:1 ratio to either receive the sodium-glucose co-transporter 2 inhibitor (SGLT2i) Dapagliflozin (10mg/day) or Placebo on top of recommended standard therapy for in total 12 weeks. The results of this study may provide new mechanistic insight into the beneficial effects of Dapagliflozin on volume regulation and vascular function and have great potential to contribute to change current clinical guidelines in the management of patients with heart failure.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dapagliflozin Dapagliflozin Dapagliflozin tablet (10mg/tablet), orally, once daily for 12 weeks. Placebo Placebo Placebo tablet, matching Dapglilflozin, orally, once daily for 12 weeks.
- Primary Outcome Measures
Name Time Method Change in relative plasma volume status (PVS). Change between baseline (0 weeks) and after 2, 6 and 12 weeks of treatment. Change in relative plasma volume status (PVS) from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The plasma volume (PV) will be measured via optimized CO-rebreathing technique.
- Secondary Outcome Measures
Name Time Method Change in red blood cell volume (RBCV). Change between baseline (0 weeks) and after 2, 6 and 12 weeks of treatment. Change in RBCV from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The RBCV will be measured via optimized CO-rebreathing technique.
Change in extracellular to total body water ratio (ECW/TBW). Change between baseline (0 weeks) and after 2, 6 and 12 weeks of treatment. Change in ECW/TBW ratio from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The ECW/TBW ratio will be measured via direct segmental multi-frequency bioelectrical impedance analaysis (DSM-BIA).
Change in intracellular to total body water ratio (ICW/TBW). Change between baseline (0 weeks) and after 2, 6 and 12 weeks of treatment. Change in ICW/TBW ratio from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The ICW/TBW ratio will be measured via direct segmental multi-frequency bioelectrical impedance analaysis (DSM-BIA).
Change in total hemoglobin mass (Hbmass). Change between baseline (0 weeks) and after 2, 6 and 12 weeks of treatment. Change in Hbmass from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The Hbmass will be measured via optimized CO-rebreathing technique.
Change in flicker-light induced retinal arteriolar dilatation (FIDa). Change between baseline (0 weeks) and after 12 weeks of treatment. Change in FIDa from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The FIDa will be measured via dynamic retinal vessel analysis (DVA).
Change in retinal arterial to venous ratio (AVR). Change between baseline (0 weeks) and after 12 weeks of treatment. Change in AVR from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The AVR will be measured via static retinal vessel analysis (SVA).
Change in pulse wave velocity (PWV). Change between baseline (0 weeks) and after 12 weeks of treatment. Change in PWV from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The PWV as measure of arterial stiffness (AS) will be assessed via planar tonometry pulse wave analysis (PWA).
Change in flow-mediated dilatation (FMD) of the brachial artery. Change between baseline (0 weeks) and after 12 weeks of treatment. Change in FMD from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The FMD as measure of endothelial function will be assessed via arm sonography and short-term cuff-mediated arm ischemia.
Change in glyceryl-trinitrate-(GTN) induced dilatation of the brachial artery. Change between baseline (0 weeks) and after 12 weeks of treatment. Change in GTN-induced dilatation of the brachial artery from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The GTN-induced dilatation of the brachial artery will be measured via arm sonography and sublingual GTN-puff.
Change in blood volume (BV). Change between baseline (0 weeks) and after 2, 6 and 12 weeks of treatment. Change in BV from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The BV will be measured via optimized CO-rebreathing technique.
Change in flicker-light induced retinal venular dilatation (FIDv). Change between baseline (0 weeks) and after 12 weeks of treatment. Change in FIDv from baseline to 12 weeks of dapagliflozin treatment in comparison to placebo will be assessed. The FIDv will be measured via dynamic retinal vessel analysis (DVA).
Trial Locations
- Locations (1)
University Heart Center Zurich
🇨🇭Zurich, Switzerland