Pharmacokinetics of Bisoprolol and SGLT2i in Acutely Decompensated Heart Failure (BISO-ADHF)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Drug: Recompensation (guideline directed medical therapy)

• Study Type: Observational
• Enrollment (Estimated): 12

Contacts and Locations

Study Locations

• Germany
  • Homburg, Germany, 66421
    • Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, University Hospital Saarland, Saarland University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting with acute decompensated heart failure (ADHF) at the intensive care unit at Saarland University Medical Center

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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)	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.
Patients after recompensation; Same patients after recompensation. (phase B) After resolution of the signs of congestion (mainly achieved by intravenous diuretics and/or vasodilators but no requirement for positive inotropic drugs such as catecholamines or levosimendan), as evidenced by the following: A decrease in body weight and; Resolution of the physical findings (absence of signs) of congestion, including resolution of the physical findings of congestion including peripheral edema and rales on pulmonary examination (chest X-ray) according to the clinical judgment of the attending physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic assessment (blood pressure in mmHg) of patients in decompensated and recompensated state	Pharmacodynamics of Bisoprolol and Dapagliflozin and Empagliflozin	up to 7 days
Hemodynamic assessment (heart rate in bpm) of patients in decompensated and recompensated state	Pharmacodynamics of Bisoprolol and Dapagliflozin and Empagliflozin	up to 7 days

Collaborators and Investigators

• Sponsor: Universität des Saarlandes

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 29, 2024
• First Submitted That Met QC Criteria: June 4, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Bisoprolol; Acute Decompensated Heart Failure; SGLT2-inhibitors
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: BISO-ADHF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No