Acute Decompensated Heart Failure
Conditions
Keywords
Acute Decompensated Heart Failure, Bisoprolol, SGLT2-inhibitors, Pharmacokinetics, Pharmacodynamics
Brief summary
The pharmacokinetics (PK) and pharmacodynamics (PD) of bisoprolol and sodium-glucose co-transporter-2 inhibitors (SGLT2i, dapagliflozin and empagliflozin) in patients with acutely decompensated heart failure (ADHF), compared to the recompensated state, is unknown. If not in cardiogenic shock (no need of vasopressor (catechoalmines) therapy or other inotropic support), established oral betablocker therapy should de continued. Whether this holds true for SGLT2i in ADHF is less clear but current evidence suggest safety and potentially beneficial effects in doing so. To the best of our knowledge, no data regarding PK/PD are available for the most widely used beta blocker bisoprolol and the newly approved/in Germany available SGLT2i Dapagliflozin and Empagliflozin. This study shall provide first evidence on the PK/PD-profile of p.o. bisoprolol and SGLT2i (dapaglifozin or empagliflozin) regarding acute (hemodynamic) effects and safety as well as to provide data on dose recommendations eventually in patients with ADHF.
Interventions
DRUGRecompensation (guideline directed medical therapy)
Recompensation mainly achieved by intravenous diuretics and/or vasodilators but no requirement for positive inotropic drugs such as catecholamines or levosimendan.
Sponsors
Universität des Saarlandes
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
* Patients with decompensated heart failure caused by heart failure irrespective of ejection fraction (heart failure with reduced, mildly reduced or preserved ejection fraction and de-novo heart failure) * Signs of decompensation: peripheral edema, jugular venous distension, pulmonary rales, protodiastolic gallop rhythm, ascites, or demonstration of pulmonary venous congestion on chest X-ray * Previous documented beta blocker therapy * elevated natriuretic peptides (nt-pro-BNP ≥125 pg/ml) * patients admitted to the intensive care unit
Exclusion criteria
* Left ventricular or biventricular assist device therapy * Cardiogenic shock * need of vasopressor (catechoalmines) therapy or other inotropic support (dobutamine or levosimendan) * Clinical symptomatic hypotension * Bradycardia (\<50 bpm) * patients requiring dialysis (CVVHD) * Inflammatory bowel disease (eg, M. Crohn or Colitis ulcerosa) * Not able to give written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration [Cmax in ng/ml] of Bisoprolol/ Dapagliflozin/ Empaglifozin | up to 7 days | toxicological measurements (using liquid chromatography coupled to high-resolution mass spectrometry) of drug levels in venous blood in decompensated and recompensated state (Comparison decompensated and recompensated state) |
| Plasma Concentration (in ng/ml) over time of Bisoprolol/ Dapaglifozin/ Empagliflozin (AUC= Area under the curve) | up to 7 days | toxicological measurements (using liquid chromatography coupled to high-resolution mass spectrometry) of drug levels in venous blood in decompensated and recompensated state (Comparison decompensated and recompensated state) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemodynamic assessment (blood pressure in mmHg) of patients in decompensated and recompensated state | up to 7 days | Pharmacodynamics of Bisoprolol and Dapagliflozin and Empagliflozin |
| Hemodynamic assessment (heart rate in bpm) of patients in decompensated and recompensated state | up to 7 days | Pharmacodynamics of Bisoprolol and Dapagliflozin and Empagliflozin |
Countries
Germany
Outcome results
None listed