Heart FailureSNPsNCT03122834
Effect of Genetic Polymorphism on the Clinical Outcome of Patients With Heart Failure
An observational study of Heart Failure, run by Ain Shams University at 1 site in Egypt.
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)… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- How many people
- 246 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Apr 2020to 14 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Adult, Older adult
Study population: Heart Failure Patients with reduced Ejection Fraction
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Keywords
- Heart Failure, Genetic Polymorphism, RAAS, Cardiac Fibrosis, Remodeling
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
RAAS genes and Clinical Outcome
Association between RAAS genetic polymorphism and clinical response, in-terms of change in LVEF among patients with heart failure
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months
RAAS genes and Biomarkers
Association between RAAS genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Measured: 6 months
Adrenergic receptors genes and Biomarkers
Association between Adrenergic receptors genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Measured: 6 months
Cardiac Fibrosis genes and Clinical Outcome
Association between Cardiac Fibrosis genes genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Measured: 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.
Measured: 6 months
Secondary outcomes (1)
Patients' mortality
Potential interaction between these target genes polymorphism and the 1 Year patients' mortality.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2017
- Study start15 Apr 2020
- Primary completion10 Apr 2024
- Study completion14 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 246 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Collaborators
- Misr International University, National Heart Institute
- Responsible party
- Principal investigator, Neven Sarhan, Misr International University
- Investigators
- Neven M. Sarhan, PhD, Principal investigator, Misr International UniversityMona F. Schaalan, PhD, Study director, Misr International UniversityBassem Zarif, MD, Study chair, National Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03122834
- Sponsor's protocol ID
- SGLT2i-MRAs-ARNI
- Acronym
- SNPs
- Status last verified
- Feb 2025
- First submitted
- 14 Apr 2017
- Last updated
- 20 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Genetic Polymorphism on the Clinical Outcome, Echocardiographic Parameters and Cardiac Biomarkers of Patients With Heart Failure
- ClinicalTrials.gov ID
- NCT03122834
- Acronym / sponsor ID
- SNPs / SGLT2i-MRAs-ARNI
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Genetic Polymorphism, RAAS, Cardiac Fibrosis, Remodeling
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 246 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Collaborators
- Misr International University, National Heart Institute
- Study start
- 15 Apr 2020 (actual)
- Primary completion
- 10 Apr 2024 (actual)
- Study completion
- 14 Jun 2024 (actual)
- First posted
- 21 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Heart Failure Patients with reduced Ejection Fraction
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
RAAS genes and Clinical Outcome
Time frame: 6 months
Association between RAAS genetic polymorphism and clinical response, in-terms of change in LVEF among patients with heart failure
Adrenergic receptors genes and Clinical Outcome
Time frame: 6 months
Association between Adrenergic receptors genetic polymorphism and clinical response in terms of change in LVEF among patients with heart failure.
Cardiac Fibrosis genes and Clinical Outcome
Time frame: 6 months
Association between Cardiac Fibrosis genes genetic polymorphism and clinical response in terms of change in LVEF among patients with heart failure.
Reno-protective effect and gene polymorphism
Time frame: 6 months
Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal response in-terms of change in GFR among patients with heart failure.
RAAS genes and Biomarkers
Time frame: 6 months
Association between RAAS genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Adrenergic receptors genes and Biomarkers
Time frame: 6 months
Association between Adrenergic receptors genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Cardiac Fibrosis genes and Clinical Outcome
Time frame: 6 months
Association between Cardiac Fibrosis genes genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Other Gene polymorphisms and Renal biomarkers
Time frame: 6 months
Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal biomarkers among patients with heart failure.
1 secondary outcome
Patients' mortality
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neven M. Sarhan, PhD principal investigator
Misr International University
Mona F. Schaalan, PhD study director
Misr International University
Bassem Zarif, MD study chair
National Heart Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RAAS genes and Clinical Outcome (time frame: 6 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2025; AzTrials last refreshed its copy on 8 Nov 2026.