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

2018年6月25日 更新者:Neven Sarhan、Ain Shams University

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

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.

研究概览

地位

完全的

条件

详细说明

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.

研究类型

观察性的

注册 (实际的)

157

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Cairo、埃及
        • Ain Shams University

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 80年 (成人、年长者)

接受健康志愿者

不适用

有资格学习的性别

全部

取样方法

概率样本

研究人群

Heart Failure Patients with reduced Ejection Fraction

描述

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.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

队列和干预

团体/队列
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) for the first time.
Cohort B
Heart Failure patients who are candidate for add-on treatment with Spironolactone / Eplerenone.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
RAAS genes and Clinical Outcome
大体时间:6 months
Association between RAAS genetic polymorphism and clinical response, Cardiac remodeling and Fibrosis biomarkers and echocardiographic outcome of patients with heart failure.
6 months
Adrenergic receptors genes and Clinical Outcome
大体时间:6 months
Association between Adrenergic receptors genetic polymorphism and clinical response, Cardiac remodeling and Fibrosis biomarkers and echocardiographic outcome of patients with heart failure.
6 months
Cardiac Fibrosis genes and Clinical Outcome
大体时间:6 months
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

次要结果测量

结果测量
措施说明
大体时间
Overall patients' clinical outcome
大体时间:12 months
Potential interaction between these target genes polymorphism and the overall patients' clinical outcome, mortality and response to treatment of heart failure.
12 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Neven M. Sarhan, MSc、Misr International University
  • 学习椅:Nagwa A. Sabri, PhD、Ain Shams University
  • 研究主任:Mona F. Schaalan, PhD、Misr International University
  • 研究主任:Lamiaa M. Elwakeel, PhD、Ain Shams University
  • 研究主任:Hazem M. Khorshid, MD、Ain Shams University
  • 研究主任:Mohamed H. Solyaman, PhD、Ain Shams University

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2017年4月15日

初级完成 (实际的)

2018年4月10日

研究完成 (实际的)

2018年6月14日

研究注册日期

首次提交

2017年4月14日

首先提交符合 QC 标准的

2017年4月20日

首次发布 (实际的)

2017年4月21日

研究记录更新

最后更新发布 (实际的)

2018年6月26日

上次提交的符合 QC 标准的更新

2018年6月25日

最后验证

2018年6月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • ASUPhd45

药物和器械信息、研究文件

研究美国 FDA 监管的药品

研究美国 FDA 监管的设备产品

在美国制造并从美国出口的产品

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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