Pharmacokinetics of Bisoprolol and SGLT2i in Acutely Decompensated Heart Failure

NCT06453577 | Active Not Recruiting

• 1 other identifier: BISO-ADHF
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Decompensated Heart Failure

Keywords

Acute Decompensated Heart Failure; Bisoprolol; SGLT2-inhibitors; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Hemodynamic assessment (blood pressure in mmHg) of patients in decompensated and recompensated state

  up to 7 days

• Hemodynamic assessment (heart rate in bpm) of patients in decompensated and recompensated state

  up to 7 days

Study Arms (2)

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)

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: 1. A decrease in body weight and 2. 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.

Interventions

Recompensation (guideline directed medical therapy) DRUG

Recompensation mainly achieved by intravenous diuretics and/or vasodilators but no requirement for positive inotropic drugs such as catecholamines or levosimendan.

Patients with acute decompensated heart failure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universität des Saarlandes: lead

Study Sites (1)

Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, University Hospital Saarland, Saarland University

Homburg, 66421, Germany

Location

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2024
• First Posted: June 11, 2024
• Study Start: May 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)