Pharmacokinetics of Bisoprolol and SGLT2i in Acutely Decompensated Heart Failure

Acute Decompensated Heart Failure Clinical Trial

— BISO-ADHF  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06453577
• Other study ID #: BISO-ADHF
• Status: Recruiting
• Start date: May 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Universität des Saarlandes
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure

Intervention

Drug:
• Recompensation (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.

Locations

Country	Name	City	State
Germany	Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, University Hospital Saarland, Saarland University	Homburg

Sponsors (1)

Lead Sponsor	Collaborator
Universität des Saarlandes

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration [Cmax in ng/ml] of Bisoprolol/ Dapagliflozin/ Empaglifozin	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)	up to 7 days
Primary	Plasma Concentration (in ng/ml) over time of Bisoprolol/ Dapaglifozin/ Empagliflozin (AUC= Area under the curve)	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)	up to 7 days
Secondary	Hemodynamic assessment (blood pressure in mmHg) of patients in decompensated and recompensated state	Pharmacodynamics of Bisoprolol and Dapagliflozin and Empagliflozin	up to 7 days
Secondary	Hemodynamic assessment (heart rate in bpm) of patients in decompensated and recompensated state	Pharmacodynamics of Bisoprolol and Dapagliflozin and Empagliflozin	up to 7 days