Determination of Drug Levels for Pharmacotherapy of Heart Failure

NCT06035978 | Not Yet Recruiting Phase 4

• 1 other identifier: FNO-HeFa1-BESPISAVA
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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).

Conditions

Cardiovascular Diseases; Heart Failure With Reduced Ejection Fraction

Keywords

Cardiovascular Diseases; Heart Failure with Reduced Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Determination of the rate of significance between the serum concentration of the used medicinal products and the dose of this medicinal product

  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 Outcomes (8)

• Clinical indicator - NT-proBNP concentration

  24 month

• Clinical indicator - 6-minute walk test

  24 month

• Clinical indicator - Minnesota Living With Heart Failure Questionnaire

  24 month

• Clinical indicator - Echocardiographic examination

  24 month

• Clinical indicator - The hospitalization for HFrEF

  24 month

Study Arms (1)

Patients with Heart Failure with Reduced Ejection Fraction

EXPERIMENTAL

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; Drug: Valsartan and Sacubitril; Drug: Carvedilol; Drug: Bisoprolol; Drug: Metoprolol; Drug: Spironolactone

Interventions

Nebivolol DRUG

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

Also known as: Nebilet, anatomical-therapeutic-chemical code (ATC) C07AB12

Patients with Heart Failure with Reduced Ejection Fraction

Valsartan and Sacubitril DRUG

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

Also known as: Entresto, ATC C09DX04

Patients with Heart Failure with Reduced Ejection Fraction

Carvedilol DRUG

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

Also known as: Dilatrend, ATC C07AG02

Patients with Heart Failure with Reduced Ejection Fraction

Bisoprolol DRUG

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

Also known as: Concor, ATC C07AB07

Patients with Heart Failure with Reduced Ejection Fraction

Metoprolol DRUG

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

Also known as: Betaloc ZOK, ATC C07AB02

Patients with Heart Failure with Reduced Ejection Fraction

Spironolactone DRUG

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

Also known as: Verospiron, ATC C03DA01

Patients with Heart Failure with Reduced Ejection Fraction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Ostrava: lead

Study Sites (1)

University Hospital Ostrava

Ostrava, Czech Republic, 70852, Czechia

Location

Related Publications (13)

• Buda V, Prelipcean A, Cozma D, Man DE, Negres S, Scurtu A, Suciu M, Andor M, Danciu C, Crisan S, Dehelean CA, Petrescu L, Rachieru C. An Up-to-Date Article Regarding Particularities of Drug Treatment in Patients with Chronic Heart Failure. J Clin Med. 2022 Apr 4;11(7):2020. doi: 10.3390/jcm11072020.

  PMID: 35407628 BACKGROUND

• Raschi E, Diemberger I, Sabatino M, Poluzzi E, De Ponti F, Potena L. Evaluating sacubitril/valsartan as a treatment option for heart failure with reduced ejection fraction and preserved ejection fraction. Expert Opin Pharmacother. 2022 Feb;23(3):303-320. doi: 10.1080/14656566.2022.2027909. Epub 2022 Jan 20.

  PMID: 35050813 BACKGROUND

• Pyvovar SM, Rudyk IS. Use of beta-blockers in patients with heart failure - unresolved issues. Pol Merkur Lekarski. 2022 Aug 23;50(298):237-239.

  PMID: 36086982 BACKGROUND

• Lee CM, Kang P, Cho CK, Park HJ, Lee YJ, Bae JW, Choi CI, Kim HS, Jang CG, Lee SY. Physiologically based pharmacokinetic modelling to predict the pharmacokinetics of metoprolol in different CYP2D6 genotypes. Arch Pharm Res. 2022 Jun;45(6):433-445. doi: 10.1007/s12272-022-01394-2. Epub 2022 Jun 28.

  PMID: 35763157 BACKGROUND

• Fontana V, Turner RM, Francis B, Yin P, Putz B, Hiltunen TP, Ruotsalainen S, Kontula KK, Muller-Myhsok B, Pirmohamed M. Chromosomal Region 11p14.1 is Associated with Pharmacokinetics and Pharmacodynamics of Bisoprolol. Pharmgenomics Pers Med. 2022 Mar 22;15:249-260. doi: 10.2147/PGPM.S352719. eCollection 2022.

  PMID: 35356681 BACKGROUND

• de Denus S, Leclair G, Dube MP, St-Jean I, Zada YF, Oussaid E, Jutras M, Givertz MM, Mentz RJ, Tang WHW, Ferreira JP, Rouleau J, Butler J, Kalogeropoulos AP. Spironolactone metabolite concentrations in decompensated heart failure: insights from the ATHENA-HF trial. Eur J Heart Fail. 2020 Aug;22(8):1451-1461. doi: 10.1002/ejhf.1802. Epub 2020 Apr 1.

  PMID: 32237012 BACKGROUND

• Giri P, Joshi V, Giri S, Delvadia P, Jain MR. Simultaneous determination of sacubitrilat and fimasartan in rat plasma by a triple quad liquid chromatography-tandem mass spectrometry method utilizing electrospray ionization in positive mode. Biomed Chromatogr. 2021 Feb;35(2):e4981. doi: 10.1002/bmc.4981. Epub 2020 Sep 18.

  PMID: 32895916 BACKGROUND

• Iacoviello M, Pugliese R, Correale M, Brunetti ND. Optimization of Drug Therapy for Heart Failure With Reduced Ejection Fraction Based on Gender. Curr Heart Fail Rep. 2022 Dec;19(6):467-475. doi: 10.1007/s11897-022-00583-w. Epub 2022 Oct 5.

  PMID: 36197626 BACKGROUND

• Ritscher S, Georges C, Wunder C, Wallemacq P, Persu A, Toennes SW. Assessment of adherence to diuretics and beta-blockers by serum drug monitoring in comparison to urine analysis. Blood Press. 2020 Oct;29(5):291-298. doi: 10.1080/08037051.2020.1763775. Epub 2020 May 13.

  PMID: 32400211 BACKGROUND

• Rea F, Iorio A, Barbati G, Bessi R, Castrichini M, Nuzzi V, Scagnetto A, Senni M, Corrao G, Sinagra G, Di Lenarda A. Patient adherence to drug treatment in a community based-sample of patients with chronic heart failure. Int J Cardiol. 2022 Feb 15;349:144-149. doi: 10.1016/j.ijcard.2021.11.018. Epub 2021 Nov 18. No abstract available.

  PMID: 34801616 BACKGROUND

• Sweeney M, Cole GD, Pabari P, Hadjiphilippou S, Tayal U, Mayet J, Chapman N, Plymen CM. Urinary drug metabolite testing in chronic heart failure patients indicates high levels of adherence with life-prolonging therapies. ESC Heart Fail. 2021 Jun;8(3):2334-2337. doi: 10.1002/ehf2.13284. Epub 2021 Mar 11.

  PMID: 33709563 BACKGROUND

• Simpson J, Jackson CE, Haig C, Jhund PS, Tomaszewski M, Gardner RS, Tsorlalis Y, Petrie MC, McMurray JJV, Squire IB, Gupta P. Adherence to prescribed medications in patients with heart failure: insights from liquid chromatography-tandem mass spectrometry-based urine analysis. Eur Heart J Cardiovasc Pharmacother. 2021 Jul 23;7(4):296-301. doi: 10.1093/ehjcvp/pvaa071.

  PMID: 32597982 BACKGROUND

• Jelinek L, Vaclavik J, Ramik Z, Pavlu L, Benesova K, Jarkovsky J, Lazarova M, Janeckova H, Spurna J, Taborsky M. Directly Measured Adherence to Treatment in Chronic Heart Failure: LEVEL-CHF Registry. Am J Med Sci. 2021 Apr;361(4):491-498. doi: 10.1016/j.amjms.2020.12.004. Epub 2020 Dec 7.

  PMID: 33781390 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Nebivolol; sacubitril and valsartan sodium hydrate drug combination; Carvedilol; Bisoprolol; Metoprolol; Spironolactone

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Propanolamines; Propanols; Carbazoles; Indoles; Heterocyclic Compounds, 3-Ring; Phenoxypropanolamines; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Marie Lazárová, MD, Ph.D.

  University Hospital Ostrava

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiří Hynčica

CONTACT

0042059737; jiri.hyncica@fno.cz

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: September 13, 2023
• Study Start: March 1, 2024
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)