Determination of Drug Levels for Pharmacotherapy of Heart Failure

January 17, 2024 updated by: University Hospital Ostrava

Use of Determination of Drug Levels to Optimize Pharmacotherapy of Heart Failure

The aim of this study is to determine whether and how serum concentrations of the used medicinal products, including their metabolites, correlate with selected clinical indicators of heart failure (NT-proBNP concentration, 6-minute walk test, quality of life questionnaire, echocardiographic parameters, hospitalization for HFrEF, length of survival).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The prevalence of chronic heart failure increases with age, and this disease is one of the most common reasons for hospitalization in the elderly. In order to reduce the number of exacerbations, the frequency of hospitalizations, morbidity and mortality and improve the overall quality of life, the treatment strategy should be individually set for each patient, regularly monitored and reviewed.

Patients with chronic heart failure show significant differences in the pharmacokinetics of both cardiovascular and non-cardiovascular drugs. At the same time, they tend to be exposed to other prescribed medicinal products, and therefore there is an increased risk of drugs interactions. These findings emphasize the need for comprehensive pharmacokinetic studies in patients with chronic heart failure, together with the exploration of the potential benefit of biomarkers suitable for monitoring the clinical status of patients. Pharmacotherapy of chronic heart failure with reduced ejection fraction (Heart Failure with Reduced Ejection Fraction - HFrEF) currently consists of beta-blockers together with mineralocorticoid receptor antagonists, the combination of sacubitril/valsartan drugs and sodium-glucose transporter 2 inhibitors. Although the recommendation of therapeutic drug monitoring (TDM) in patients with chronic heart failure has not yet been established, its introduction can serve as an effective tool for detecting changes in the pharmacokinetics of drugs used, objectifying drug interactions and ascertaining patient adherence to treatment, thereby becoming part of safe personalized pharmacotherapy of this disease.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 4

Contacts and Locations

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

Study Contact

Study Locations

  • Czechia
    • Czech Republic
      • Ostrava, Czech Republic, Czechia, 70852
        • University Hospital Ostrava
        • Contact:
        • Principal Investigator:
          • Marie Lazárová, MD, Ph.D.
        • Sub-Investigator:
          • Ivana Kacířová, doc., MD, Ph.D.

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • HFrEF with already established or newly started treatment with the listed medicinal products
  • Male and female patients over 18 years of age
  • Signed Informed Consent with participation in the study
  • Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) result at baseline and use an acceptable method of contraception with a home control urine pregnancy test every 3 months throughout the duration of the study

Exclusion Criteria:

  • Hypersensitivity to the medicinal substance or to any auxiliary substance
  • Pregnant and breastfeeding women
  • Additional exclusion criteria for patients taking Bisoprolol, Carvedilol, Metoprolol succinate or Nebivolol: Unstable or decompensated heart failure belonging to New York Heart Association (NYHA) group IV according to the New York Heart Association classification, requiring intravenous inotropic support
  • Additional exclusion criteria for patients using Bisoprolol, Carvedilol, Metoprolol succinate or Nebivolol:
  • - Clinically manifest liver dysfunction
  • - History of bronchospasm or asthma
  • - Severe obstructive airways disease
  • - 2nd and 3rd degree A-V block (unless a permanent pacemaker is implanted)
  • - severe bradycardia (heart rate <50)
  • - 2nd and 3rd degree A-V block (unless a permanent pacemaker is implanted)
  • - severe bradycardia (heart rate <50)
  • - cardiogenic shock
  • - sinus node dysfunction syndrome (including sinoatrial block)
  • - severe hypotension (systolic blood pressure <85 mmHg)
  • - Prinzmetal angina
  • - untreated pheochromocytoma
  • - metabolic acidosis
  • - severe peripheral arterial circulation disorders
  • - concurrent intravenous treatment with verapamil or diltiazem
  • Additional exclusion criteria for patients using Spironolactone:
  • - anuria
  • - acute renal failure
  • - severe renal impairment (estimated glomerular filtration rate <10 ml/min)
  • - hyperkalemia >5.5 mmol/l
  • - hyponatremia <125 mmol/l
  • - Addison's disease
  • - concurrent use of eplerenone or other potassium-sparing diuretics
  • - porphyria
  • Additional exclusion criteria for patients using Sacubitril/Valsartan:
  • - concomitant use with Angiotensin converting enzyme (ACE) inhibitors
  • - angioedema related to previous ACE inhibitor treatment or a history of angiotensin II receptor blockers (ARB) treatment
  • - hereditary or idiopathic angioedema
  • - concomitant use with medicinal products containing Aliskiren in patients with diabetes mellitus or in patients with impaired renal function (eGFR <60 ml/min/1.73 m2)
  • - severe liver dysfunction, biliary cirrhosis and cholestasis

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with Heart Failure with Reduced Ejection Fraction
Patients with heart failure with reduced ejection fraction, aged 18+, dispensary at the Cardiology Outpatient Clinic for Heart Failure University Hospital Ostrava, who are orally administered tablets one of the evaluated medicinal products or their combination as indicated by the attending physician (Nebivolol, Valsartan and Sacubitril, Carvedilol, Bisoprolol, Metoprolol, Spironolactone).
Drug: Nebivolol
Nebivolol (Nebilet) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.
Other Names:
  • Nebilet, anatomical-therapeutic-chemical code (ATC) C07AB12
Drug: Valsartan and Sacubitril
Valsartan and Sacubitril (Entresto) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.
Other Names:
  • Entresto, ATC C09DX04
Drug: Carvedilol
Carvedilol (Dilatrend) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.
Other Names:
  • Dilatrend, ATC C07AG02
Drug: Bisoprolol
Bisoprolol (Concor) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.
Other Names:
  • Concor, ATC C07AB07
Drug: Metoprolol
Metoprolol (Betaloc ZOK) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.
Other Names:
  • Betaloc ZOK, ATC C07AB02
Drug: Spironolactone
Verospiron (Spironolactone) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.
Other Names:
  • Verospiron, ATC C03DA01

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the rate of significance between the serum concentration of the used medicinal products and the dose of this medicinal product
Time Frame: 24 month
Determination whether the serum concentration of used medicinal products (Nebivolol, Valsartan/Sacubitril, Carvedilol, Bisoprolol, Metoprolol, Spironolactone) is more important than the dose of these medicinal products for compensating health status in patients with chronic heart failure with reduced ejection fraction (HFrEF).
24 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical indicator - NT-proBNP concentration
Time Frame: 24 month
Determination of a significant dependence between serum concentration of the used medicinal products and the values of the selected clinical indicator - N-terminal prohormone of natriuretic peptide B (NT-pro BNP), measured in pg/ml.
24 month
Clinical indicator - 6-minute walk test
Time Frame: 24 month
Determination of a significant dependence between the serum concentration of the used medicinal products and the values of the selected clinical indicator - 6-minute walking test. The test measures the distance the patient walks 6 minutes in the corridor (in meters).
24 month
Clinical indicator - Minnesota Living With Heart Failure Questionnaire
Time Frame: 24 month
Determination of a significant dependence between the serum concentration of the used medicinal products and the values of the selected clinical indicator - Minnesota Living With Heart Failure Questionnaire. The total score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of life.
24 month
Clinical indicator - Echocardiographic examination
Time Frame: 24 month
Determination of a significant dependence between the serum concentration of the used medicinal products and the values of the selected clinical indicator - echocardiographic examination.
24 month
Clinical indicator - The hospitalization for HFrEF
Time Frame: 24 month
Determination of a significant dependence between the serum concentration of the used medicinal products and the values of the selected clinical indicator - the hospitalization for HFrEF (yes/no).
24 month
Clinical indicator - The length of survival
Time Frame: 24 month
Determination of a significant dependence between the serum concentration of the used medicinal products and the values of the selected clinical indicator - the length of survival (measured in month).
24 month
Adverse effects
Time Frame: 24 month
Determination of the number of patients in whom a significant dependence between the serum concentration of the used medicinal products and the adverse effects of these medicinal products is demonstrated.
24 month
Non-adherence to treatment
Time Frame: 24 month
Determination the number of patients in whom non-adherence to treatment will be demonstrated.
24 month

Collaborators and Investigators

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

Sponsor

University Hospital Ostrava

Investigators

  • Principal Investigator: Marie Lazárová, MD, Ph.D., University Hospital Ostrava

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 (Estimated)

March 1, 2024

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

April 1, 2026

Study Registration Dates

First Submitted

September 6, 2023

First Submitted That Met QC Criteria

September 6, 2023

First Posted (Actual)

September 13, 2023

Study Record Updates

Last Update Posted (Actual)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 17, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FNO-HeFa1-BESPISAVA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to share individual participant data with other researchers.

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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