Bisoprolol Plasma Residual Concentrations in Chronic Heart Failure

Heart Failure With Reduced Ejection Fraction Clinical Trial

— PREVALENT  

Official title:

Bisoprolol Plasma Residual Concentrations for the Optimization of Drug Management in Heart Failure With Mild to Reduced Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03644446
• Other study ID #: DC-2016-2725
• Status: Recruiting
• Start date: November 2, 2017
• Est. completion date: November 2, 2020

Study information

• Verified date: July 2018
• Source: University Hospital, Caen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: November 2, 2020
• Est. primary completion date: November 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Biological:
• Bisoprolol plasma residual concentration dosage
Bisoprolol plasma residual concentration dosage will be subsequently studied by renal function (altered if creatinine clearance < 30mL/min, mild altered between 30-60mL/min, normal > 60mL/min as estimated by the CKD-EPI formula)

Locations

Country	Name	City	State
France	Alexandre Joachim	Caen	Basse Normandie

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Caen

Country where clinical trial is conducted

France, 

References & Publications (28)

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bisoprolol residual plasma concentration by dose and renal function	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.	At the time of inclusion
Secondary	Clinical parameters at the time of inclusion	Heart rate in beats per minute (bpm). Heart rate will be studied as a continous outcome and as a dichotomous outcome for efficacy. The efficacy parameter cutoff is a heart rate < 70bpm.	At the time of inclusion
Secondary	Clinical parameters at the time of inclusion	Systolic and diastolic blood pressure (in mmHg)	At the time of inclusion
Secondary	Clinical parameters at the time of inclusion	Tolerance : presence of any new symptom that requires a dose lowering or discontinuation of bisoprolol (dichotomous outcome) or symptomatic orthostatic hypotension	At the time of inclusion
Secondary	Clinical parameters at 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.	At the time of inclusion
Secondary	Biological assessment	Routine biological evaluation : creatinine (in µmol/L)	At the time of inclusion
Secondary	Biological assessment	Routine biological evaluation : Brain Natriuretic Peptide (in pg/mL)	At the time of inclusion
Secondary	Biological assessment	Galectin-3 (in ng/mL)	At the time of inclusion
Secondary	Clinical outcomes at one year	Heart failure symptoms worsening (dichotomous variable)	At one year follow-up
Secondary	Clinical outcomes at one year	Hospitalization for heart failure (dichotomous variable)	At one year follow-up
Secondary	Clinical outcomes at one year	Death from any cause (dichotomous variable)	At one year follow-up
Secondary	Clinical outcomes at one year	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).	At one year follow-up