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

NCT ID: NCT03122834

Last Updated: 2025-02-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 246 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-04-15
• Study Completion Date: 2024-06-14

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.

Detailed Description

In the past decade there has been considerable progress in cardiovascular pharmacogenetics and pharmacogenomics. Although drug response variation in Heart Failure is likely multifactorial, pharmacogenetic variation may partially account for therapeutic failure contributing to the remaining high mortality in HF. Identifying novel gene variants affecting treatment response may reveal unrecognized pathways and new potential therapeutic targets. Few studies to date have attempted to assess the extent to which variation in drug response was exclusively due to genetic factors and therefore expounding the likely clinical benefit of using pharmacogenetics to guide HF therapy. One of the prerequisites to bridging this gap is to consider likely trial designs and criteria that will lead to a consensus upon using pharmacogenetics-based variants to guide therapy in clinical practice.

Another area gaining momentum is tailoring medication in response to biomarker levels as there is considerable evidence for the relationship between remodeling and fibrosis markers levels and worse prognosis in those with HF. Moreover,investigation into the proteomics of HF may also reveal variation that can be used to guide HF therapy hand-in-hand with biomarkers and pharmacogenomics, which would facilitate bridging the gap of genotype and phenotype. Disparity between genotype and phenotype may also account for the inconsistent results with current SNPs, further appreciation of this relationship would be a significant step forward.

Conditions

Heart Failure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

Cohort B

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Misr International University

OTHER

Sponsor Role: collaborator

National Heart Institute

UNKNOWN

Sponsor Role: collaborator

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Neven Sarhan

Lecturer of Clinical Pharmacy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Neven M. Sarhan, PhD

Role: PRINCIPAL_INVESTIGATOR

Misr International University

Mona F. Schaalan, PhD

Role: STUDY_DIRECTOR

Misr International University

Bassem Zarif, MD

Role: STUDY_CHAIR

National Heart Institute

Locations

National Heart Institute

Cairo, , Egypt

Countries

Egypt

Other Identifiers

SGLT2i-MRAs-ARNI

Identifier Type: -

Identifier Source: org_study_id