Clinical trial NCT05536271: Pharmacogenetic Study of Bisoprolol in Egyptian Patients With Acute Coronary Syndrome
Official title: Pharmacogenetic Study of Bisoprolol in Egyptian Patients With Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Coronary Syndrome
Lead sponsor: Damanhour University
Sponsor class: OTHER
Collaborators: name: Alexandria University
First posted: 2022-09-10
Enrollment: 127
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 1. Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
2. All participants should agree to take part in this clinical study and will provide informed consent.
3. Over 100 patients diagnosed with acute coronary syndrome for whom bisoprolol therapy is prescribed , will be recruited from Alexandria university hospital.
4. whole blood samples will be collected for Analyses of CYP2D6 and CYP3A4 variant alleles.
5. Blood samples for plasma concentration measurements of bisoprolol will be drawn at steady-state peak levels after 2-4 hours of administration of bisoprolol.
6. Heart rate and blood pressure of the patients will be measured to assess the clinical effect of bisoprolol.
7. Echocardiogram will be obtained at baseline and after 1-3 months of therapy with bisoprolol to assess the effect of the drug on ventricular Remodeling.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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.

Primary outcomes:
measure: CYP2D6 gene polymorphism
timeFrame: 2 months
measure: CYP3A5 gene polymorphism
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Damanhūr
country: Egypt
facility: Damanhour University
state: Behira
Study officials:
affiliation: Clinical Pharmacy Specialist, Damanhour University.
name: Sherouk Okda, Bachelor
role: PRINCIPAL_INVESTIGATOR
affiliation: Lecturer of Clinical Pharmacy, Damanhour University.
name: amira B kassem, PHD
role: STUDY_DIRECTOR
affiliation: Lecturer of biochemisrty, Damanhour University.
name: ahmad salahaldin, PHD
role: STUDY_DIRECTOR
affiliation: cardiologist , alexandria university
name: ahmad alamrawy, PHD
role: STUDY_CHAIR
affiliation: Lecturer of Clinical Pharmacy, Damanhour University.
name: noha ahmad, PHD
role: STUDY_CHAIR
affiliation: Lecturer of Analytical chemistry, Damanhour University.
name: sohila Alonsy, PHD
role: STUDY_CHAIR
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