Effect of Genetic Polymorphism on the Clinical Outcome of Patients With Heart Failure

NCT03122834 | Completed

• 1 other identifier: SGLT2i-MRAs-ARNI
• Study Type: observational
• Target: 246
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure (HF) is one the most common cause of hospitalization and represents the end stage of a variety of heart conditions; it is associated with significant morbidity and mortality.The pathophysiology of HF is centered on increased activity in the adrenergic and renin-angiotensin-aldosterone systems (RAAS), which leads to vasoconstriction and fluid restriction with further deleterious effect on cardiac function. Β-blockers, angiotensin converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) and aldosterone antagonists reduce activity in these pathways and have shown prognostic benefit, thus are the foundation of HF therapy.There is a growing body of evidence that variation in proteins within the sympathetic axis and RAAS influence drug response thus increasingly pharmacogenetics of HF research is being sought as a way to optimize HF treatment and advance new drug development in this area.

Conditions

Heart Failure

Keywords

Heart Failure; Genetic Polymorphism; RAAS; Cardiac Fibrosis; Remodeling

Outcome Measures

Primary Outcomes (8)

• RAAS genes and Clinical Outcome

  Association between RAAS genetic polymorphism and clinical response, in-terms of change in LVEF among patients with heart failure

  6 months

• Adrenergic receptors genes and Clinical Outcome

  Association between Adrenergic receptors genetic polymorphism and clinical response in terms of change in LVEF among patients with heart failure.

  6 months

• Cardiac Fibrosis genes and Clinical Outcome

  Association between Cardiac Fibrosis genes genetic polymorphism and clinical response in terms of change in LVEF among patients with heart failure.

  6 months

• Reno-protective effect and gene polymorphism

  Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal response in-terms of change in GFR among patients with heart failure.

  6 months

• RAAS genes and Biomarkers

  Association between RAAS genetic polymorphism and Cardiac biomarkers among patients with heart failure.

  6 months

• Adrenergic receptors genes and Biomarkers

  Association between Adrenergic receptors genetic polymorphism and Cardiac biomarkers among patients with heart failure.

  6 months

• Cardiac Fibrosis genes and Clinical Outcome

  Association between Cardiac Fibrosis genes genetic polymorphism and Cardiac biomarkers among patients with heart failure.

  6 months

• Other Gene polymorphisms and Renal biomarkers

  Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal biomarkers among patients with heart failure.

  6 months

Secondary Outcomes (1)

• Patients' mortality

  12 months

Study Arms (2)

Cohort A

Newly diagnosed Heart Failure patients who will be treated with beta blockers (BB) and Angiotensin converting enzyme inhibitors (ACEIs)/or Angiotensin receptor blockers (ARBs) /or Angiotensin receptor neprilysin inhibitors (ARNI) and sodium glucose transporter 2 inhibitor (SGLT2i) for the first time.

Cohort B

Heart Failure patients who are candidate for add-on treatment with Spironolactone / Eplerenone.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Heart Failure Patients with reduced Ejection Fraction

You may qualify if:

• Heart failure patients NYHA class II to IV.
• Left ventricular ejection fraction (LVEF) \< 45%
• Written informed consent of the subject to participate in the study.
• Newly diagnosed patients who will be treated with BBs and ACEIs/or ARBs.
• Patients who are candidate for add-on treatment with Spironolactone / Eplerenone.
• Age of 18 years to 80 years.

You may not qualify if:

• Contraindication to SGLT2i.
• Contraindication to Spironolactone / Eplerenone.
• Patients who received previous treatment with Spironolactone / Eplerenone.
• Sig CAD, CABG, PCI, or valve surgery within 3 months.
• Mild-to-severe valvular stenosis or severe (grade III/IV) valvular regurgitation
• Pregnant or nursing women.

Sponsors & Collaborators

• Ain Shams University: lead
• Misr International University: collaborator
• National Heart Institute: collaborator

Study Sites (1)

National Heart Institute

Cairo, Egypt

Location

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood samples will be collected and stored in - 20°C environment for DNA extraction by DNA extraction kit according to manufacturer recommendation.

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Neven M. Sarhan, PhD

  Misr International University

  PRINCIPAL INVESTIGATOR

• Mona F. Schaalan, PhD

  Misr International University

  STUDY DIRECTOR

• Bassem Zarif, MD

  National Heart Institute

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Clinical Pharmacy

Study Record Dates

• First Submitted: April 14, 2017
• First Posted: April 21, 2017
• Study Start: April 15, 2020
• Primary Completion: April 10, 2024
• Study Completion: June 14, 2024
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

EG (1)