Impact of Body Composition on Bisoprolol and Ramipril Pharmacokinetics in Patients With Chronic Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to determine if cachexia and changes in body composition influence pharmacokinetics of bisoprolol and ramipril and the accuracy of equations for renal function estimation.

Detailed Description
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Patients with chronic heart failure on treatment with bisoprolol and/or ramipril will be included. Study will consist of two study visits: baseline visit (V1) and visit which will be performed at least 6 months after baseline (V2). At both visits same procedures will be performed. On the day of the visit, patients will be asked to take their morning dose of bisoprolol and/or ramipril after the withdrawal of the first morning plasma sample. Additional 3 to 5 plasma samples will be taken within 5 hours post bisoprolol and/or ramipril dose in order to determine pharmacokinetic profile of both drugs. Body composition will be measured by bioimpedance and dual-energy X-ray absorptiometry. Renal function will be measured by clearance of intravenously administered iohexol. Biochemical parameters, muscle strength, fatigue and anorexia will be assessed in order to determine presence of cachexia. Changes in body composition will be correlated with changes in pharmacokinetic parameters of bisoprolol and ramipril. Pharmacokinetic parameters in cachectic patients will be compared to pharmacokinetic parameters in non-cachectic patients. Parameters of body composition will be correlated with the difference between measured and estimated renal function.

Official Title
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Impact of Body Composition Changes and Cachexia on Bisoprolol and Ramipril Pharmacokinetics and Renal Function Estimation in Patients With Chronic Heart Failure

Conditions
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Chronic Heart Failure, Cachexia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic heart failure of New York Heart Association Functional Classification (NYHA) class II and III On treatment with bisoprolol for at least 3 days and/or ramipril for at least 4 days before V1 Able and willing to provide freely given written informed consent Exclusion Criteria: Chronic renal disease with estimated glomerular filtration rate calculated by Modification of Diet in Renal Disease (MDRD) equation < 40 mL/(min x 1,73 m2) at V1 or V2 Liver disease or increased serum liver enzymes (bilirubin > 1.5 x normal, gamma-glutamyl transpeptidase (GGT) > 2.5 x normal, aspartate transaminase (AST) > 2.5 x normal, alanine transaminase (ALT) > 2.5 x normal) at V1 or V2 Absence of bisoprolol or ramipril steady state concentrations at V1 or V2 or withdrawal of bisoprolol and/or ramipril in-between both visits Acute decompensation of heart failure in less than 4 weeks before V1 or V2 Addition, withdrawal or change in dose of drugs that importantly influence bisoprolol or ramipril pharmacokinetics in-between V1 and V2 Unable to understand and comply with protocol or to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic heart failure patients<br>Patients with chronic heart failure who attend to internal medicine outpatient clinic. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of bisoprolol and ramipril | Pharmacokinetic parameters of bisoprolol and ramipril(clearance, volume of distribution, area under concentration-time curve, maximal concentration, time to maximal concentration) will be determined. The relation between pharmacokinetic parameters and body composition/cachexia will be assessed. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Body composition (percentage and amount of body fat, lean body mass, dry lean body mass and body water) will be measured by bioimpedance and dual energy X-ray absorptiometry | Baseline and 6 months | 
| Cachexia diagnosis | Cachexia diagnosis (determination of low body mass index, wasting, biochemical parameters, muscle strength, fatigue and anorexia) | Baseline and 6 months | 
| Renal function | Renal function will be measured by clearance of intravenously applied iohexol. Estimation of renal function will be calculated with different equations based on serum creatinine concentration. Measured and estimated renal function will be compared and the differences related to body composition parameters. | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic heart failure, Bisoprolol, Ramipril, Pharmacokinetic, Cachexia, Body composition, Renal function, Iohexol