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

Heart Failure Clinical Trial

— SNPs  

Official title:

Effect of Genetic Polymorphism on the Clinical Outcome, Echocardiographic Parameters and Cardiac Biomarkers of Patients With Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03122834
• Other study ID #: ASUPhd45
• Status: Completed
• Start date: April 15, 2017
• Est. completion date: June 14, 2018

Study information

• Verified date: June 2018
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: June 14, 2018
• Est. primary completion date: April 10, 2018
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 BBsor ACEIs.

• 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.

Related Conditions & MeSH terms

• Heart Failure

Locations

Country	Name	City	State
Egypt	Ain Shams University	Cairo

Sponsors (2)

Lead Sponsor	Collaborator
Ain Shams University	Misr International University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RAAS genes and Clinical Outcome	Association between RAAS genetic polymorphism and clinical response, Cardiac remodeling and Fibrosis biomarkers and echocardiographic outcome of patients with heart failure.	6 months
Primary	Adrenergic receptors genes and Clinical Outcome	Association between Adrenergic receptors genetic polymorphism and clinical response, Cardiac remodeling and Fibrosis biomarkers and echocardiographic outcome of patients with heart failure.	6 months
Primary	Cardiac Fibrosis genes and Clinical Outcome	Association between Cardiac Fibrosis genes genetic polymorphism and clinical response, Cardiac remodeling and Fibrosis biomarkers and echocardiographic outcome of patients with heart failure.	6 months
Secondary	Overall patients' clinical outcome	Potential interaction between these target genes polymorphism and the overall patients' clinical outcome, mortality and response to treatment of heart failure.	12 months