Determination of Drug Levels for Pharmacotherapy of Heart Failure

NCT ID: NCT06035978

Last Updated: 2024-01-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2026-04-30

Brief Summary

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).

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.

Conditions

Cardiovascular Diseases; Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

Carvedilol (Dilatrend) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Bisoprolol

Intervention Type: DRUG

Bisoprolol (Concor) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Metoprolol

Intervention Type: DRUG

Metoprolol (Betaloc ZOK) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Spironolactone

Intervention Type: DRUG

Verospiron (Spironolactone) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Nebivolol

Intervention Type: DRUG

Nebivolol (Nebilet) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Valsartan and Sacubitril

Intervention Type: DRUG

Valsartan and Sacubitril (Entresto) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Interventions

Carvedilol

Carvedilol (Dilatrend) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Intervention Type: DRUG

Bisoprolol

Bisoprolol (Concor) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Intervention Type: DRUG

Metoprolol

Metoprolol (Betaloc ZOK) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Intervention Type: DRUG

Spironolactone

Verospiron (Spironolactone) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Intervention Type: DRUG

Nebivolol

Nebivolol (Nebilet) tablet will be administered orally to patients according to their clinical condition and the decision of the attending physician.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Nebilet, anatomical-therapeutic-chemical code (ATC) C07AB12; Entresto, ATC C09DX04; Dilatrend, ATC C07AG02; Concor, ATC C07AB07; Betaloc ZOK, ATC C07AB02; Verospiron, ATC C03DA01

Eligibility Criteria

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
• - 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
• - 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
• - 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Ostrava

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie Lazárová, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Ostrava

Locations

University Hospital Ostrava

Ostrava, Czech Republic, Czechia

Countries

Czechia

Central Contacts

Jiří Hynčica

Role: CONTACT

jiri.hyncica@fno.cz

0042059737 ext. 2587

Facility Contacts

Jiří Hynčica

Role: primary

jiri.hyncica@fno.cz

0042059737 ext. 2587

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Other Identifiers

FNO-HeFa1-BESPISAVA

Identifier Type: -

Identifier Source: org_study_id