Dapagliflozin on Volume Vascular Outcomes. (DAPA-VOLVO)

Frank Ruschitzka

Status and phase: Completed; Phase 4

Conditions: Heart Failure，Congestive

Treatments: Drug: Dapagliflozin; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04869124

ESR-20-20601

2020-004143-89 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female, age of 18 or older;
2. Patients with documented diagnosis of chronic or de novo heart failure (NYHA II-IV) and clinically stabilized (considered for hospital discharge) after hospitalization/ ambulatory care because of an acute decompensated (congestive) heart failure (ADHF) event;
3. eGFR ≥ 30 mL/min/1.73 m2 (CKD-EPI formula) at enrolment;
4. Provision of signed informed consent prior to any study specific procedure;

Exclusion criteria

1. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product;
2. Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor;
3. Participation in another study with investigational drug within the 30 days preceding and during the present study;
4. Type 1 diabetes mellitus;
5. Symptomatic hypotension or systolic blood pressure <90 mmHg at 2 out of 3 measurements either at visit 1 or visit 2;
6. Coronary revascularization (percutaneous coronary intervention because of STEMI or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization;
7. Implantation of a CRT device within 12 weeks prior to enrolment or intent to implant a CRT device during 12 weeks of study observation period if indicated according to the actual guidelines [11];
8. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization;
9. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic obstructive cardiomyopathy or uncorrected primary valvular disease;
10. Symptomatic bradycardia or second or third degree heart block without a pacemaker;
11. Severe (eGFR <20 mL/min/1.73 m2 by CKD-EPI), unstable or rapidly progressing renal disease;
12. Women who are pregnant or breast feeding;
13. Intention to become pregnant during the course of the study;
14. Known or suspected non-compliance, drug or alcohol abuse;
15. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant;
16. Patients with severely restricted liver function;
17. Patients with recurrent mycotic genital infections;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 2 patient groups, including a placebo group

Dapagliflozin

Active Comparator group

Description:

Dapagliflozin tablet (10mg/tablet), orally, once daily for 12 weeks.

Treatment:

Drug: Dapagliflozin

Placebo

Placebo Comparator group

Description:

Placebo tablet, matching Dapglilflozin, orally, once daily for 12 weeks.

Treatment:

Drug: Placebo