Pharmacogenetic Study of Bisoprolol in Egyptian Patients With Acute Coronary Syndrome

NCT05536271 | Completed Phase 2

• 1 other identifier: BisoprololPG
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

Acute coronary syndrome (ACS) is any group of clinical symptoms compatible with acute myocardial ischemia and includes unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). (1). In Egypt, the overall prevalence of coronary heart disease (CHD) is 8.3 % (2). In addition, CHD in Egypt is the principal cause of death, responsible for 21.73% of total mortality (2). Beta-blockers have shown to reduce the short-term risk of a reinfarction and the long-term risk of all-cause mortality and cardiovascular mortality (3). Beta blockers are used within 24 hours of ACS and given as long-term therapy after discharge (4). The Most frequently used drug in Egypt is bisoprolol. In patients with myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous betablocker before reperfusion reduced infarct size and increased left ventricular ejection fraction (4). Despite the established benefits of beta blockers in ACS (acute coronary syndrome patients), they showed interindividual variability in patient's' blood pressure and heart rate (5). pharmacokinetic variability was found in bisoprolol response especially in elderly patients (6). Bisoprolol is eliminated in equal parts by hepatic metabolism by CYP2D6 and CYP3A4 enzymes and by the kidney(7). A possible cause for this variability may be due to CYP450 genetic polymorphism. The CYP450 activity ranges considerably within a population and includes ultrarapid metabolizers (UMs), extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs) (8).The proposed research in this application will investigate the correlation between CYP2D6 and CYP3A4 polymorphism and pharmacokinetics of bisoprolol and will investigate the impact of the Genes' polymorphism on the clinical effect of bisoprolol in patients with acute coronary syndrome.

Conditions

Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (2)

• CYP2D6 gene polymorphism

  CYP2D6 gene polymorphism

  2 months

• CYP3A5 gene polymorphism

  CYP3A5 gene polymorphism

  2 months

Study Arms (1)

Acute coronary syndrome patients

EXPERIMENTAL

Acute coronary syndrome patients prescribed with bisoprolol

Drug: Bisoprolol Fumarate

Interventions

Bisoprolol Fumarate DRUG

antihypertensive medicine prescribed for acute coronary syndrome patients

Also known as: concor

Acute coronary syndrome patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted with chest pain suspected to have ACS (acute coronary syndrome).
• Both with ST elevation (STEMI) and without ST elevation (N-STEMI ) and unstable angina.
• HR \> 50 bpm.
• Systolic Blood pressure \> 90 mmHg.

You may not qualify if:

• Patients with contraindications to Bisoprolol therapy:
• Heart rate \<60 bpm
• Systolic blood pressure \<90 mmHg
• Moderate or severe left ventricular failure
• Shock
• heart block
• Active asthma/reactive airways disease.

Sponsors & Collaborators

• Damanhour University: lead
• Alexandria University: collaborator

Study Sites (1)

Damanhour University

Damanhūr, Behira, 22511, Egypt

Location

Related Publications (7)

• Almahmeed W, Arnaout MS, Chettaoui R, Ibrahim M, Kurdi MI, Taher MA, Mancia G. Coronary artery disease in Africa and the Middle East. Ther Clin Risk Manag. 2012;8:65-72. doi: 10.2147/TCRM.S26414. Epub 2012 Feb 16.

  PMID: 22368447 BACKGROUND

• Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction; Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24. No abstract available.

  PMID: 22922414 BACKGROUND

• Ibanez B, Macaya C, Sanchez-Brunete V, Pizarro G, Fernandez-Friera L, Mateos A, Fernandez-Ortiz A, Garcia-Ruiz JM, Garcia-Alvarez A, Iniguez A, Jimenez-Borreguero J, Lopez-Romero P, Fernandez-Jimenez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vazquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Perez de Prado A, Fernandez-Campos MJ, Casado I, Garcia-Rubira JC, Garcia-Prieto J, Sanz-Rosa D, Cuellas C, Hernandez-Antolin R, Albarran A, Fernandez-Vazquez F, de la Torre-Hernandez JM, Pocock S, Sanz G, Fuster V. Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial. Circulation. 2013 Oct 1;128(14):1495-503. doi: 10.1161/CIRCULATIONAHA.113.003653. Epub 2013 Sep 3.

  PMID: 24002794 BACKGROUND

• Agesen FN, Weeke PE, Tfelt-Hansen P, Tfelt-Hansen J; for ESCAPE-NET. Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology. Pharmacol Res Perspect. 2019 Jul 12;7(4):e00496. doi: 10.1002/prp2.496. eCollection 2019 Aug.

  PMID: 31338197 BACKGROUND

• Taguchi M, Nozawa T, Igawa A, Inoue H, Takesono C, Tahara K, Hashimoto Y. Pharmacokinetic variability of routinely administered bisoprolol in middle-aged and elderly Japanese patients. Biol Pharm Bull. 2005 May;28(5):876-81. doi: 10.1248/bpb.28.876.

  PMID: 15863897 BACKGROUND

• Tjandrawinata RR, Setiawati E, Yunaidi DA, Santoso ID, Setiawati A, Susanto LW. Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects. Drug Des Devel Ther. 2012;6:311-6. doi: 10.2147/DDDT.S36567. Epub 2012 Oct 30.

  PMID: 23139624 BACKGROUND

• Mohammed Alkreathy H, Mohammed Eid Alsayyid K, Alaama JY, Al Ghalayini K, Karim S, Esmat A, Damanhouri ZA. Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study. Saudi J Biol Sci. 2020 Oct;27(10):2727-2732. doi: 10.1016/j.sjbs.2020.06.022. Epub 2020 Jun 20.

  PMID: 32994732 BACKGROUND

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Bisoprolol

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Sherouk Okda, Bachelor

  Clinical Pharmacy Specialist, Damanhour University.

  PRINCIPAL INVESTIGATOR

• amira B kassem, PHD

  Lecturer of Clinical Pharmacy, Damanhour University.

  STUDY DIRECTOR

• ahmad salahaldin, PHD

  Lecturer of biochemisrty, Damanhour University.

  STUDY DIRECTOR

• ahmad alamrawy, PHD

  cardiologist , alexandria university

  STUDY CHAIR

• noha ahmad, PHD

  Lecturer of Clinical Pharmacy, Damanhour University.

  STUDY CHAIR

• sohila Alonsy, PHD

  Lecturer of Analytical chemistry, Damanhour University.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 10, 2022
• Study Start: September 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: August 16, 2022
• Last Updated: June 7, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)