Bisoprolol Plasma Residual Concentrations in Chronic Heart Failure (PREVALENT)

August 21, 2018 updated by: University Hospital, Caen

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

81

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Basse Normandie
      • Caen, Basse Normandie, France, 14000
        • Recruiting
        • Alexandre Joachim

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Consecutive ambulatory chronic HFrEF patients followed at the CHU de Caen, treated with maximum tolerated dose of bisoprolol. Patients can benefit of other HFrEF recommended treatment at the exception of ivabradine that would confound the bisoprolol effect on heart rate. Patients 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) and bisoprolol dose (5, 7.5 or 10mg).

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Bisoprolol 5mg
Chronic 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.
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)
Bisoprolol 7.5mg
Chronic 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.
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)
Bisoprolol 10mg
Chronic 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.
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bisoprolol residual plasma concentration by dose and renal function
Time Frame: At 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.
At the time of inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical parameters at the time of inclusion
Time Frame: 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
Clinical parameters at the time of inclusion
Time Frame: At the time of inclusion
Systolic and diastolic blood pressure (in mmHg)
At the time of inclusion
Clinical parameters at the time of inclusion
Time Frame: 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
Clinical parameters at the time of inclusion
Time Frame: 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
Biological assessment
Time Frame: At the time of inclusion
Routine biological evaluation : creatinine (in µmol/L)
At the time of inclusion
Biological assessment
Time Frame: At the time of inclusion
Routine biological evaluation : Brain Natriuretic Peptide (in pg/mL)
At the time of inclusion
Biological assessment
Time Frame: At the time of inclusion
Galectin-3 (in ng/mL)
At the time of inclusion
Clinical outcomes at one year
Time Frame: At one year follow-up
Heart failure symptoms worsening (dichotomous variable)
At one year follow-up
Clinical outcomes at one year
Time Frame: At one year follow-up
Hospitalization for heart failure (dichotomous variable)
At one year follow-up
Clinical outcomes at one year
Time Frame: At one year follow-up
Death from any cause (dichotomous variable)
At one year follow-up
Clinical outcomes at one year
Time Frame: At 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).
At one year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Caen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 2, 2017

Primary Completion (Anticipated)

November 2, 2019

Study Completion (Anticipated)

November 2, 2020

Study Registration Dates

First Submitted

August 13, 2018

First Submitted That Met QC Criteria

August 21, 2018

First Posted (Actual)

August 23, 2018

Study Record Updates

Last Update Posted (Actual)

August 23, 2018

Last Update Submitted That Met QC Criteria

August 21, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DC-2016-2725

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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