Clinical trial NCT03122834: Effect of Genetic Polymorphism on the Clinical Outcome of Patients With Heart Failure
Official title: Effect of Genetic Polymorphism on the Clinical Outcome, Echocardiographic Parameters and Cardiac Biomarkers of Patients With Heart Failure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Keywords: Heart Failure
Genetic Polymorphism
RAAS
Cardiac Fibrosis
Remodeling
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: Misr International University
name: National Heart Institute
First posted: 2017-04-21
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Heart Failure Patients with reduced Ejection Fraction

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.

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.

Primary outcomes:
measure: RAAS genes and Clinical Outcome
timeFrame: 6 months
measure: Adrenergic receptors genes and Clinical Outcome
timeFrame: 6 months
measure: Cardiac Fibrosis genes and Clinical Outcome
timeFrame: 6 months
measure: Reno-protective effect and gene polymorphism
timeFrame: 6 months
measure: RAAS genes and Biomarkers
timeFrame: 6 months
measure: Adrenergic receptors genes and Biomarkers
timeFrame: 6 months
measure: Cardiac Fibrosis genes and Clinical Outcome
timeFrame: 6 months
measure: Other Gene polymorphisms and Renal biomarkers
timeFrame: 6 months
Secondary outcomes:
measure: Patients' mortality
timeFrame: 12 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: National Heart Institute
Study officials:
affiliation: Misr International University
name: Neven M. Sarhan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Misr International University
name: Mona F. Schaalan, PhD
role: STUDY_DIRECTOR
affiliation: National Heart Institute
name: Bassem Zarif, MD
role: STUDY_CHAIR
References: