Heart Failure - NYHA II - IVNCT06901609
Effect of Genetic Polymorphism on the Clinical Outcome to SGLT2 Inhibitors in Heart Failure Patients
An observational study of Heart Failure - NYHA II - IV and Cardiac Fibrosis, run by Ain Shams University at 1 site in Egypt.
Trial summary
Heart failure with reduced ejection fraction (HFrEF) is a significant cause of morbidity and mortality. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated efficacy in improving renal outcomes in patients with HFrEF. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure - NYHA II - IV, Cardiac Fibrosis, Cardiac Remodeling
- What is being tested?
- SGLT2 inhibitor (Dapagliflozin 10mg)
- How many people
- 200 participants
- Where
- 1 siteEgypt
- Study dates
- 22 Nov 2023to 1 Jul 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Heart Failure patients with reduced ejection fraction (LVEF<40%)
Who may be able to join
- Adults (≥18 years) with HFrEF (LVEF ≤40%).
- Initiation of SGLT2 inhibitor therapy.
- Stable background HF therapy for at least 4 weeks.
- Written informed consent for participation and genetic testing.
Who cannot join
- Known hypersensitivity to SGLT2 inhibitors.
- History of ketoacidosis or recurrent urinary tract infections.
- End-stage renal disease (eGFR <30 mL/min/1.73 m²).
- Life expectancy <6 months due to non-cardiovascular conditions.
- Pregnancy or lactation.
Trial locations and contacts
1 site in 1 country.
About this study
Heart failure with reduced ejection fraction (HFrEF) is a significant cause of morbidity and mortality. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated efficacy in improving renal outcomes in patients with HFrEF. Pharmacogenetics, the study of how genetic variations influence drug response, could elucidate inter-individual variability in treatment outcomes. This study aims to assess the impact of specific genetic variants on renal outcomes in HFrEF patients treated with SGLT2 inhibitors.
Read the detailed description
Heart failure is broadly classified into two main types based on the left ventricular ejection fraction (LVEF): heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). HFpEF is characterized by a preserved or relatively normal LVEF, typically equal to or greater than 50%, despite signs and symptoms of heart failure. In contrast, HFrEF is defined by a reduced LVEF, typically less than or equal to 40%. [4] Accurate categorization of HF into HFpEF or HFrEF enables healthcare providers to implement targeted therapeutic approaches.
The intricate nature of heart failure necessitates a comprehensive approach to its diagnosis and management, given its varying presentations and underlying mechanisms. Heart injury, precipitated by diverse causes such as myocardial infarction, hypertension, and cardiomyopathies, triggers a complex and deleterious process of pathological remodeling and fibrosis within the cardiac tissue. This progressive cascade of events ultimately leads to the manifestation of heart failure. The pathophysiological mechanisms driving this progression are multifaceted, involving intricate cellular responses, neurohormonal activation, and inflammatory pathways. The initial insult, such as ischemic injury from myocardial infarction or chronic pressure overload from hypertension, sets in motion a series of maladaptive responses within the myocardium. These responses include cardiomyocyte hypertrophy, interstitial fibrosis, and alterations in extracellular matrix composition, which collectively impair myocardial contractility and promote ventricular dysfunction over time.
SGLT2 inhibitors, initially developed to manage blood glucose levels in patients with type 2 diabetes, now form part of the latest therapeutic strategies for heart failure as outlined in the 2022 AHA guidelines. This class, which includes empagliflozin, canagliflozin and dapagliflozin, has been shown to significantly reduce hospitalizations for heart failure and cardiovascular mortality in patients with symptomatic chronic HFrEF, irrespective of the presence of type 2 diabetes. Empagliflozin, a specific SGLT2I, has been particularly studied for its cardio-renal protective effects. Research by Miyata et al. (2021) has revealed that Empagliflozin goes beyond glycemic control by exerting beneficial effects on inflammatory and fibrotic markers.
- Being tested
- SGLT2 inhibitor (Dapagliflozin 10mg)
- Keywords
- SGLT2 inhibitors, Heart Failure with reduced ejection fraction, Cardiac Remodeling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SGLT2 inhibitor (Dapagliflozin 10mg)Drug
Renal response after 6 months of Dapagliflozin therapy among patients with heart failure reduced ejection fraction.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Newly diagnosed Heart Failure patients with reduced ejection fraction who are candidate for add-on treatment with sodium glucose transporter 2 inhibitor (SGLT2i) for the first time in addition to standard heart failure therapy. Receives: Drug: SGLT2 inhibitor (Dapagliflozin 10mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Secondary outcomes (1)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2025
- Study start22 Nov 2023
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure - NYHA II - IVStudies 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
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart Institute, Egypt, Misr International University, Princess Nourah Bint Abdulrahman University
- Responsible party
- Principal investigator, Neven Sarhan, Misr International University
- Investigators
- Bassem Zarif, MD, Study chair, National Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06901609
- Sponsor's protocol ID
- SGLT2 INHIBITORS
- Status last verified
- Mar 2025
- First submitted
- 24 Mar 2025
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Genetic Polymorphism on the Clinical Outcome to SGLT2 Inhibitors in Heart Failure Patients
- ClinicalTrials.gov ID
- NCT06901609
- Acronym / sponsor ID
- SGLT2 INHIBITORS
- Keywords
- SGLT2 inhibitors, Heart Failure with reduced ejection fraction, Cardiac Remodeling
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Collaborators
- National Heart Institute, Egypt, Misr International University, Princess Nourah Bint Abdulrahman University
- Study start
- 22 Nov 2023 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jul 2025 (estimated)
- First posted
- 30 Mar 2025 (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 with reduced ejection fraction (HFrEF) is a significant cause of morbidity and mortality. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated efficacy in improving renal outcomes in patients with HFrEF. Pharmacogenetics, the study of how genetic variations influence drug response, could elucidate inter-individual variability in treatment outcomes. This study aims to assess the impact of specific genetic variants on renal outcomes in HFrEF patients treated with SGLT2 inhibitors.
Detailed description
Heart failure is broadly classified into two main types based on the left ventricular ejection fraction (LVEF): heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). HFpEF is characterized by a preserved or relatively normal LVEF, typically equal to or greater than 50%, despite signs and symptoms of heart failure. In contrast, HFrEF is defined by a reduced LVEF, typically less than or equal to 40%. [4] Accurate categorization of HF into HFpEF or HFrEF enables healthcare providers to implement targeted therapeutic approaches.
The intricate nature of heart failure necessitates a comprehensive approach to its diagnosis and management, given its varying presentations and underlying mechanisms. Heart injury, precipitated by diverse causes such as myocardial infarction, hypertension, and cardiomyopathies, triggers a complex and deleterious process of pathological remodeling and fibrosis within the cardiac tissue. This progressive cascade of events ultimately leads to the manifestation of heart failure. The pathophysiological mechanisms driving this progression are multifaceted, involving intricate cellular responses, neurohormonal activation, and inflammatory pathways. The initial insult, such as ischemic injury from myocardial infarction or chronic pressure overload from hypertension, sets in motion a series of maladaptive responses within the myocardium. These responses include cardiomyocyte hypertrophy, interstitial fibrosis, and alterations in extracellular matrix composition, which collectively impair myocardial contractility and promote ventricular dysfunction over time.
SGLT2 inhibitors, initially developed to manage blood glucose levels in patients with type 2 diabetes, now form part of the latest therapeutic strategies for heart failure as outlined in the 2022 AHA guidelines. This class, which includes empagliflozin, canagliflozin and dapagliflozin, has been shown to significantly reduce hospitalizations for heart failure and cardiovascular mortality in patients with symptomatic chronic HFrEF, irrespective of the presence of type 2 diabetes. Empagliflozin, a specific SGLT2I, has been particularly studied for its cardio-renal protective effects. Research by Miyata et al. (2021) has revealed that Empagliflozin goes beyond glycemic control by exerting beneficial effects on inflammatory and fibrotic markers.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort A | – | Drug: SGLT2 inhibitor (Dapagliflozin 10mg)Newly diagnosed Heart Failure patients with reduced ejection fraction who are candidate for add-on treatment with sodium glucose transporter 2 inhibitor (SGLT2i) for the first time in addition to standard heart failure therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Heart Failure patients with reduced ejection fraction (LVEF<40%)
Key inclusion criteria (4 listed)
- Adults (≥18 years) with HFrEF (LVEF ≤40%).
- Initiation of SGLT2 inhibitor therapy.
- Stable background HF therapy for at least 4 weeks.
- Written informed consent for participation and genetic testing.
Key exclusion criteria (5 listed)
- Known hypersensitivity to SGLT2 inhibitors.
- History of ketoacidosis or recurrent urinary tract infections.
- End-stage renal disease (eGFR <30 mL/min/1.73 m²).
- Life expectancy <6 months due to non-cardiovascular conditions.
- Pregnancy or lactation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SGLT2 inhibitor (Dapagliflozin 10mg)Renal response after 6 months of Dapagliflozin therapy among patients with heart failure reduced ejection fraction. | Drug | Cohort A |
Primary outcome
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.
1 secondary outcome
Gene polymorphisms and Renal biomarkers
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Individual participant dataSharing planned: Undecided
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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.
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 - NYHA II - IV and Cardiac Fibrosis, 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 4 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 30 Mar 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?
This study is still under way. Results are not available in the source record yet.
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?
Reno-protective effect and gene polymorphism (time frame: 6 months). 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 30 Mar 2025.