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

Chronic Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01829880
• Other study ID #: GOLNIK_PKT1
• Status: Recruiting
• Phase: N/A
• First received: April 8, 2013
• Last updated: April 8, 2013
• Start date: October 2011
• Est. completion date: August 2013

Study information

• Verified date: April 2013
• Source: The University Clinic of Pulmonary and Allergic Diseases Golnik
• Contact: Mitja Lainscak, MD, PhD
• Phone: (0) 4 256 9483
• Email: mitja.lainscak[@]guest.arnes.si
• Is FDA regulated: No
• Health authority: Slovenia: Ethics Committee
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: August 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cachexia
• Chronic Heart Failure
• Heart Failure

Locations

Country	Name	City	State
Slovenia	University Clinic of Respiratory and Allergic Diseases Golnik	Golnik

Sponsors (1)

Lead Sponsor	Collaborator
The University Clinic of Pulmonary and Allergic Diseases Golnik

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Cachexia diagnosis	Cachexia diagnosis (determination of low body mass index, wasting, biochemical parameters, muscle strength, fatigue and anorexia)	Baseline and 6 months	No
Secondary	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	No