Clinical trial NCT01829880: Impact of Body Composition on Bisoprolol and Ramipril Pharmacokinetics in Patients With Chronic Heart Failure
Official title: Impact of Body Composition Changes and Cachexia on Bisoprolol and Ramipril Pharmacokinetics and Renal Function Estimation in Patients With Chronic Heart Failure
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Heart Failure
Cachexia
Keywords: Chronic heart failure
Bisoprolol
Ramipril
Pharmacokinetic
Cachexia
Body composition
Renal function
Iohexol
Lead sponsor: The University Clinic of Pulmonary and Allergic Diseases Golnik
Sponsor class: OTHER
First posted: 2013-04-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with chronic heart failure who attend internal medicine outpatient clinic

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic parameters of bisoprolol and ramipril
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Body composition
timeFrame: Baseline and 6 months
measure: Cachexia diagnosis
timeFrame: Baseline and 6 months
measure: Renal function
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Golnik
country: Slovenia
facility: University Clinic of Respiratory and Allergic Diseases Golnik
Study officials:
affiliation: University Clinic Golnik
name: Mitja Lainscak, MD, PhD
role: STUDY_CHAIR
References:
citation: Cvan Trobec K, Kerec Kos M, von Haehling S, Anker SD, Macdougall IC, Ponikowski P, Lainscak M. Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure. Croat Med J. 2015 Dec;56(6):531-41. doi: 10.3325/cmj.2015.56.531.