Pharmacokinetics and Pharmacodynamics of Bisoprolol and SGLT2-Inhibitors (Dapagliflozin, Empagliflozin) in Acutely Decompensated Heart Failure BISO-ADHF (BI=BIsoprolol, SO=Sodium-glucose Co-transporter-2 Inhibitors in Acute Decompensated Heart Failure)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Maximum Plasma Concentration [Cmax in ng/ml] of Bisoprolol/ Dapagliflozin/ Empaglifozin
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Patients with acute decompensated heart failure
Patients presenting with acute decompensated heart failure (ADHF) at Saarland University Medical Center. (phase A)
ADHF (acutely decompensated CHF or new onset/ de novo HF):
Evidence of congestion and decompensation defined by physical abnormalities as follows: Physical evidence of congestion, including pitting edema > 2 mm in the lower extremities extending from the ankles to mid-calf and rales on pulmonary examination (chest X-ray)
干预措施: Recompensation (guideline directed medical therapy) (Drug)
结局指标
主要结局
Maximum Plasma Concentration [Cmax in ng/ml] of Bisoprolol/ Dapagliflozin/ Empaglifozin
时间窗: 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)
时间窗: 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)
次要结局
- Hemodynamic assessment (heart rate in bpm) of patients in decompensated and recompensated state(up to 7 days)
- Hemodynamic assessment (blood pressure in mmHg) of patients in decompensated and recompensated state(up to 7 days)