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Cardiovascular DiseasesPhase 4NCT06035978

Determination of Drug Levels for Pharmacotherapy of Heart Failure

A Phase 4 study testing Nebivolol, Valsartan and Sacubitril and Carvedilol in people with Cardiovascular Diseases and Heart Failure With Reduced Ejection Fraction, run by University Hospital Ostrava at 1 site in Czechia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nebivolol, Valsartan and Sacubitril and Carvedilol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteCzechia
Study dates
Mar 2024to Apr 2026
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 34Show fewer
  • - 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

Trial locations and contacts

1 site in 1 country.

Jiří Hynčica contact

0042059737 ext. 2587

jiri.hyncica@fno.cz

Czechia1 site

  • University Hospital Ostrava

    Ostrava, Czech Republic, 70852

    Jiří Hynčica, 0042059737 ext. 2587, jiri.hyncica@fno.cz

    Marie Lazárová, MD, Ph.D.

Other trials in Czechia

About this study

Official title: 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).

Read the 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.

Being tested
Nebivolol, Valsartan and Sacubitril, Carvedilol, Bisoprolol, Metoprolol
Keywords
Cardiovascular Diseases, Heart Failure with Reduced Ejection Fraction
Medical subject headings
Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NebivololDrug

    Also called Nebilet, anatomical-therapeutic-chemical code (ATC) C07AB12

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

  • Valsartan and SacubitrilDrug

    Also called Entresto, ATC C09DX04

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

  • CarvedilolDrug

    Also called Dilatrend, ATC C07AG02

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

  • BisoprololDrug

    Also called Concor, ATC C07AB07

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

  • MetoprololDrug

    Also called Betaloc ZOK, ATC C07AB02

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

  • SpironolactoneDrug

    Also called Verospiron, ATC C03DA01

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

Study groups in NCT06035978
Study groupRoleWhat they receive
Patients with Heart Failure with Reduced Ejection FractionExperimentalPatients 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).
Receives: Drug: Nebivolol; Drug: Valsartan and Sacubitril; Drug: Carvedilol; Drug: Bisoprolol; Drug: Metoprolol; Drug: Spironolactone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 24 month

Secondary outcomes (8)

  1. Clinical indicator - NT-proBNP concentration

    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.

    Measured: 24 month

  2. Clinical indicator - 6-minute walk test

    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).

    Measured: 24 month

  3. Clinical indicator - Minnesota Living With Heart Failure Questionnaire

    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.

    Measured: 24 month

  4. Clinical indicator - Echocardiographic examination

    Determination of a significant dependence between the serum concentration of the used medicinal products and the values of the selected clinical indicator - echocardiographic examination.

    Measured: 24 month

  5. Clinical indicator - The hospitalization for HFrEF

    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).

    Measured: 24 month

  6. Clinical indicator - The length of survival

    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).

    Measured: 24 month

  7. Adverse effects

    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.

    Measured: 24 month

  8. Non-adherence to treatment

    Determination the number of patients in whom non-adherence to treatment will be demonstrated.

    Measured: 24 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2023
  2. Study startMar 2024 (estimated)
  3. Primary completionApr 2026 (estimated)
  4. Study completionApr 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06035978
Sponsor's protocol ID
FNO-HeFa1-BESPISAVA
Status last verified
Jan 2024
First submitted
6 Sep 2023
Last updated
18 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: There is no plan to share individual participant data with other researchers.

Publications

  • 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.

    PubMed 35407628

  • 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.

    PubMed 35050813

  • 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.

    PubMed 36086982

  • 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.

    PubMed 35763157

  • 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.

    PubMed 35356681

  • 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.

    PubMed 32237012

  • 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.

    PubMed 32895916

  • 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.

    PubMed 36197626

  • 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.

    PubMed 32400211

  • 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.

    PubMed 34801616

  • 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.

    PubMed 33709563

  • 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.

    PubMed 32597982

  • 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.

    PubMed 33781390

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Nebivolol, Valsartan and Sacubitril and Carvedilol in people with Cardiovascular Diseases and Heart Failure With Reduced Ejection Fraction, run by University Hospital Ostrava at 1 site in Czechia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jiří Hynčica (0042059737 ext. 2587, jiri.hyncica@fno.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06035978, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2024.

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