Pharmacokinetics of Bisoprolol and SGLT2i in Acutely Decompensated Heart Failure

Recruiting

• Conditions: Acute Decompensated Heart Failure
• Interventions: Drug: Recompensation (guideline directed medical therapy)

• Registration Number: NCT06453577
• Lead Sponsor: Universität des Saarlandes

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-05-01
• Status Verified: 2024-05
• Study First Submitted: 2024-05-29
• Study First Submitted QC: 2024-06-04
• Study First Posted: 2024-06-11
• Last Update Submitted: 2024-06-17
• Last Update Posted: 2024-06-20
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with acute decompensated heart failure	Recompensation (guideline directed medical therapy)	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)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

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

Trial Locations

Locations (1)

Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, University Hospital Saarland, Saarland University; 🇩🇪 Homburg, Germany