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

The University Clinic of Pulmonary and Allergic Diseases Golnik60 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Chronic Heart Failure Cachexia

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

University Clinic of Respiratory and Allergic Diseases Golnik

Golnik, Slovenia

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: Baseline and 6 months

Secondary Outcomes

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

Time frame: Baseline and 6 months

Cachexia diagnosis

Cachexia diagnosis (determination of low body mass index, wasting, biochemical parameters, muscle strength, fatigue and anorexia)

Time frame: 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.

Time frame: Baseline and 6 months

Central Contacts

Mitja Lainscak, MD, PhD

CONTACT

(0) 4 256 9483 mitja.lainscak@guest.arnes.si

Katja Trobec, MPharm

CONTACT

(0) 4 256 9360 katja.trobec@klinika-golnik.si

Data from ClinicalTrials.gov

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