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Bisoprolol Plasma Residual Concentrations in Chronic Heart Failure

Conditions
Heart Failure With Reduced Ejection Fraction
Interventions
Biological: Bisoprolol plasma residual concentration dosage
Registration Number
NCT03644446
Lead Sponsor
University Hospital, Caen
Brief Summary

This study evaluate the dosage of bisoprolol plasma residual concentrations in chronic heart failure with mild to reduced ejection fraction adult patients by dose and renal function.

Detailed Description

The clinical relevance of bisoprolol plasma residual concentration in the management of HF medical therapy and the impact of renal function on reaching the maximum tolerated dose has never been studied. The investigators will perform an observational study to answer this issue.

In this study, there will be no changes of the doses of bisoprolol, whatever the bisoprolol plasma concentration, with the exception of vital threatening concentrations. This study is a pilot study.

Participants will be consecutive ambulatory chronic heart failure patients followed at the CHU de Caen, treated with maximum tolerated dose of bisoprolol with mild to reduced ejection fraction. Participants can benefit of the other heart failure recommended treatment at the exception of ivabradine that would confound the bisoprolol effect on heart rate. Participants will be subsequently studied by renal function.

Patients will be followed at one year with the electronic health record of the CHU de Caen for clinical events.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
81
Inclusion Criteria
  • Consecutive ambulatory patients with chronic heart failure with mild to reduced ejection fraction (LVEF < 50%) at the CHU de Caen
  • Aged 18 y.o. or older
  • With a stable heart failure (see exclusion criteria)
  • At the maximum tolerated dose of bisoprolol for at least one week (maximum dose reached without adverse tolerance event: orthostatic hypotension, symptomatic bradycardia, fatigue related to the treatment)
Exclusion Criteria
  • Unstable HF, that are patients who presented in the last 3 months before inclusion an hospitalization for any cardiovascular event including HF, new onset or worsening of HF or coronary artery disease symptoms
  • Patient refusing to participate
  • Patients with a non maximum tolerated dose of bisoprolol
  • Patients with ivabradine intakes
  • Body weight < 60kg or > 100kg
  • Severe liver insufficiency
  • Pregnancy
  • Liberty deprived patients

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Bisoprolol 10mgBisoprolol plasma residual concentration dosageChronic heart failure with mild to reduced ejection fraction adult patients with bisoprolol intakes at 10mg (patient's maximum tolerated dose), stable, with a left ventricular ejection fraction \< 50%. Consecutive patients at the CHU de Caen.
Bisoprolol 5mgBisoprolol plasma residual concentration dosageChronic heart failure with mild to reduced ejection fraction adult patients with bisoprolol intakes at 5mg (patient's maximum tolerated dose), stable, with a left ventricular ejection fraction \< 50%. Consecutive patients at the CHU de Caen.
Bisoprolol 7.5mgBisoprolol plasma residual concentration dosageChronic heart failure with mild to reduced ejection fraction adult patients with bisoprolol intakes at 7.5mg (patient's maximum tolerated dose), stable, with a left ventricular ejection fraction \< 50%. Consecutive patients at the CHU de Caen.
Primary Outcome Measures
NameTimeMethod
Bisoprolol residual plasma concentration by dose and renal functionAt the time of inclusion

Bisoprolol plasma residual concentrations will be performed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) with simple precipitation of proteins with acetonitrile, as described by Liu et al. The quantification will be in positive mode by multiple reaction monitoring with the following transitions: 326 to 116 for bisoprolol and 256 to 167 for diphenhydramine (control). Bisoprolol concentrations will be expressed in µg/L.

Secondary Outcome Measures
NameTimeMethod
Clinical parameters at the time of inclusionAt the time of inclusion

Tolerance : presence of a symptomatic orthostatic hypotension (dichotomous outcome) that is defined as a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with blood pressure from the sitting or supine position.

Biological assessmentAt the time of inclusion

Galectin-3 (in ng/mL)

Clinical outcomes at one yearAt one year follow-up

Bisoprolol dose modification (categorical variable : dose increased, dose decreased, dose unchanged and quantitative analysis of mean change between bisoprolol inclusion dose and bisoprolol dose at one year).

Trial Locations

Locations (1)

Alexandre Joachim

🇫🇷

Caen, Basse Normandie, France

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