Heart Failure and Reduced Ejection FractionCLEARNCT07088471
Cardiac Left Atrial Evaluation and Response in HFrEF With Sacubitril/Valsartan
An observational study of Heart Failure and Reduced Ejection Fraction, run by Connolly Hospital Blanchardstown at 1 site in Ireland.
Trial summary
Heart failure is an increasingly common condition that can have a significant impact on quality of life and reduce life expectancy. In recent decades, a number of drugs have been developed specifically for this condition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure and Reduced Ejection Fraction
- What is being tested?
- Sacubtril/Valsartan
- How many people
- 334 participants
- Where
- 1 siteIreland
- Study dates
- 1 Nov 2024to 1 Aug 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Heart Failure with reduced ejection fraction (HFrEF) patients on stable guideline-directed medical therapy prior to commencing sacubitril/valsartan (SV) will be retrospectively identified
Who may be able to join
- Adults diagnosed with heart Failure with reduced ejection fraction (HFrEF), i.e. LVEF ≤40% by Simpson's method on transthoracic echocardiography
- Stable guideline-directed medical therapy prior to sacubitril/valsartan (SV) initiation
- New York Heart Association classes II-III symptom status
- Guideline-directed up-titration of SV therapy to the maximum tolerated dose
- Transthoracic echocardiogram and NT-proBNP prior to SV initiation and at 3 months post commencement of therapy
Who cannot join
- Patients not in sinus rhythm at time of echocardiograms (precludes left atrial strain analysis)
- Sub-optimal echocardiographic images to allow measurement of left atrial strain
- Prior mitral valve intervention (left atrial strain assessment unreliable in this cohort)
- Severe mitral regurgitation (left atrial strain assessment unreliable in this cohort)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cardiac Left Atrial Evaluation and Response in HFrEF With Sacubitril/Valsartan: The CLEAR Study.
Heart failure is an increasingly common condition that can have a significant impact on quality of life and reduce life expectancy. In recent decades, a number of drugs have been developed specifically for this condition. One such drug, called Sacubitril/valsartan (SV) has been shown to reduce hospitalizations and prolong life expectancy of patients with heart failure. It works by reversing some of the structural and functional changes to the heart that occur in heart failure. However, not all patients respond to the drug. Further research is needed to better understand the reasons for this and predict who will benefit most from the drug.
Left atrial strain is a relatively new measurement that can be obtained using ultrasound imaging of the heart, and it provides objective information about how one of the heart's four chambers is functioning. The investigators aim to assess the effect of SV therapy on left atrial strain in patients with heart failure. The investigator's objective is to understand whether abnormal left atrial strain or changes in left atrial strain help predict response to SV therapy.
Read the detailed description
Sacubitril/valsartan (SV) improves cardiovascular outcomes in patients with heart failure and reduced ejection fraction (HFrEF) [1]. However, not all patients respond to therapy. SV therapy has been shown to promote reverse cardiac remodelling, which may contribute to its efficacy in responders [2].
Left atrial (LA) remodeling has been shown to be related to a variety of cardiovascular diseases. Until recently, the LA was only considered to act as a conduit for the left ventricle, and we now know that the LA plays a dynamic role throughout the cardiac cycle. Currently, LA volume is recommended by the European Society of Cardiology for the evaluation of LA size and remodeling [2]. Over the last decade, advancements in echocardiographic software have led to the development of novel parameters to measure LA function and remodeling. LA function is now divided into three phases: reservoir, conduit, and contractile phase.
Recently, speckle tracking on 2-dimensional echocardiography has been used to evaluate LA Strain. LA strain has been evaluated in clinical studies and has been shown to be a useful tool in the diagnosis of LA remodeling when compared to conventional methods. A recently published study from Korea has defined the reference ranges for LA strain in a healthy population [3]. Along with the reference range, the same study also looked at different determinants of LA strain [3]. LA strain by speckle tracking echocardiography is an affordable, non-invasive, pragmatic, diagnostic tool that can be performed as part of the standard 2D echocardiogram.
There have been limited studies assessing the relationship between SV therapy and LA strain. The investigators aim to evaluate the hypothesis that baseline LA strain and any changes associated with SV therapy may be a prognosticator of response to therapy in HFrEF patients.
- Being tested
- Sacubtril/Valsartan
- Keywords
- left atrial strain, Sacubril/valsartan, HFrEF, Heart Failure
- Medical subject headings
- Heart Failure, Systolic, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubtril/ValsartanDrug
Angiotensin-receptor blocker and neprilysin inhibitor therapy
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between pre-therapy left atrial strain parameters on speckle-tracking echocardiography and therapy-associated changes in left ventricular ejection fraction and/or serum NT-pro BNP.
Correlation between baseline, pre-therapy left atrial strain parameters on speckle-tracking echocardiography (TTE) with therapy-associated changes in left ventricular ejection fraction (LVEF) on TTE and serum NT-pro BNP. LVEF will be assessed on TTE using the modified Simpson's biplane method. Left atrial strain will be assessed using speckle tracking analysis with EchoPAC Software v204 (GE Vingmed Ultrasound AS, Horten, Norway). Correlation will be assessed using Spearman's rank correlation coefficients.
Measured: At least 3-6 months post initiation of SV therapy
Secondary outcomes (3)
Correlation between pre-therapy left atrial strain parameters and baseline left ventricular ejection fraction and serum NT-pro BNP level.
Correlation between baseline left atrial strain values and baseline left ventricular ejection fraction and NT-pro BNP. LVEF will be assessed using the modified Simpson's biplane method. Left atrial strain will be assessed using speckle tracking analysis with EchoPAC Software v204 (GE Vingmed Ultrasound AS, Horten, Norway). Correlation will be assessed using Spearman's rank correlation coefficients.
Measured: At least 3-6 months post initiation of SV therapy
Mean change in left atrial strain parameters pre- and post-SV therapy
Mean change in left atrial reservoir, conduit, and booster pump values pre- and post-SV therapy. Left atrial strain will be assessed using speckle tracking analysis with EchoPAC Software v204 (GE Vingmed Ultrasound AS, Horten, Norway).
Measured: At least 3-6 months post initiation of SV therapy
Correlation between therapy-associated changes in left atrial strain parameters and therapy-associated changes in left ventricular ejection fraction and/or serum NT pro-BNP level.
Correlation between therapy-associated changes in left atrial strain and therapy-associated changes in left ventricular ejection fraction or NT pro-BNP. LVEF will be assessed using the modified Simpson's biplane method. Left atrial strain will be assessed using speckle tracking analysis with EchoPAC Software v204 (GE Vingmed Ultrasound AS, Horten, Norway). Correlation will be assessed using Spearman's rank correlation coefficients.
Measured: At least 3-6 months post initiation of SV therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2025
- Study start1 Nov 2024
- Primary completion1 May 2025
- Study completion1 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure and Reduced Ejection FractionStudies of the same condition, open and under way.
- 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
- Case only
- Time perspective
- Retrospective
- Enrolment
- 334 participants (actual)
Sponsor and investigators
- Lead sponsor
- Connolly Hospital Blanchardstown
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael J Daly, MA MD PhD, Connolly Hospital Blanchardstown
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07088471
- Sponsor's protocol ID
- CHB 005/25
- Acronym
- CLEAR
- Status last verified
- Aug 2025
- First submitted
- 20 Jul 2025
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data can be made available upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Left Atrial Evaluation and Response in HFrEF With Sacubitril/Valsartan: The CLEAR Study.
- ClinicalTrials.gov ID
- NCT07088471
- Acronym / sponsor ID
- CLEAR / CHB 005/25
- Keywords
- left atrial strain, Sacubril/valsartan, HFrEF, Heart Failure
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 334 participants (actual)
- Lead sponsor
- Connolly Hospital BlanchardstownUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 1 May 2025 (actual)
- Study completion
- 1 Aug 2025 (actual)
- First posted
- 28 Jul 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 is an increasingly common condition that can have a significant impact on quality of life and reduce life expectancy. In recent decades, a number of drugs have been developed specifically for this condition. One such drug, called Sacubitril/valsartan (SV) has been shown to reduce hospitalizations and prolong life expectancy of patients with heart failure. It works by reversing some of the structural and functional changes to the heart that occur in heart failure. However, not all patients respond to the drug. Further research is needed to better understand the reasons for this and predict who will benefit most from the drug.
Left atrial strain is a relatively new measurement that can be obtained using ultrasound imaging of the heart, and it provides objective information about how one of the heart's four chambers is functioning. The investigators aim to assess the effect of SV therapy on left atrial strain in patients with heart failure. The investigator's objective is to understand whether abnormal left atrial strain or changes in left atrial strain help predict response to SV therapy.
Detailed description
Sacubitril/valsartan (SV) improves cardiovascular outcomes in patients with heart failure and reduced ejection fraction (HFrEF) [1]. However, not all patients respond to therapy. SV therapy has been shown to promote reverse cardiac remodelling, which may contribute to its efficacy in responders [2].
Left atrial (LA) remodeling has been shown to be related to a variety of cardiovascular diseases. Until recently, the LA was only considered to act as a conduit for the left ventricle, and we now know that the LA plays a dynamic role throughout the cardiac cycle. Currently, LA volume is recommended by the European Society of Cardiology for the evaluation of LA size and remodeling [2]. Over the last decade, advancements in echocardiographic software have led to the development of novel parameters to measure LA function and remodeling. LA function is now divided into three phases: reservoir, conduit, and contractile phase.
Recently, speckle tracking on 2-dimensional echocardiography has been used to evaluate LA Strain. LA strain has been evaluated in clinical studies and has been shown to be a useful tool in the diagnosis of LA remodeling when compared to conventional methods. A recently published study from Korea has defined the reference ranges for LA strain in a healthy population [3]. Along with the reference range, the same study also looked at different determinants of LA strain [3]. LA strain by speckle tracking echocardiography is an affordable, non-invasive, pragmatic, diagnostic tool that can be performed as part of the standard 2D echocardiogram.
There have been limited studies assessing the relationship between SV therapy and LA strain. The investigators aim to evaluate the hypothesis that baseline LA strain and any changes associated with SV therapy may be a prognosticator of response to therapy in HFrEF patients.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Heart Failure with reduced ejection fraction (HFrEF) patients on stable guideline-directed medical therapy prior to commencing sacubitril/valsartan (SV) will be retrospectively identified
Key inclusion criteria (5 listed)
- Adults diagnosed with heart Failure with reduced ejection fraction (HFrEF), i.e. LVEF ≤40% by Simpson's method on transthoracic echocardiography
- Stable guideline-directed medical therapy prior to sacubitril/valsartan (SV) initiation
- New York Heart Association classes II-III symptom status
- Guideline-directed up-titration of SV therapy to the maximum tolerated dose
- Transthoracic echocardiogram and NT-proBNP prior to SV initiation and at 3 months post commencement of therapy
Key exclusion criteria (4 listed)
- Patients not in sinus rhythm at time of echocardiograms (precludes left atrial strain analysis)
- Sub-optimal echocardiographic images to allow measurement of left atrial strain
- Prior mitral valve intervention (left atrial strain assessment unreliable in this cohort)
- Severe mitral regurgitation (left atrial strain assessment unreliable in this cohort)
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 |
|---|---|---|
| Sacubtril/ValsartanAngiotensin-receptor blocker and neprilysin inhibitor therapy | Drug | – |
Primary outcome
Correlation between pre-therapy left atrial strain parameters on speckle-tracking echocardiography and therapy-associated changes in left ventricular ejection fraction and/or serum NT-pro BNP.
Time frame: At least 3-6 months post initiation of SV therapy
Correlation between baseline, pre-therapy left atrial strain parameters on speckle-tracking echocardiography (TTE) with therapy-associated changes in left ventricular ejection fraction (LVEF) on TTE and serum NT-pro BNP. LVEF will be assessed on TTE using the modified Simpson's biplane method. Left atrial strain will be assessed using speckle tracking analysis with EchoPAC Software v204 (GE Vingmed Ultrasound AS, Horten, Norway). Correlation will be assessed using Spearman's rank correlation coefficients.
3 secondary outcomes
Correlation between pre-therapy left atrial strain parameters and baseline left ventricular ejection fraction and serum NT-pro BNP level.
Time frame: At least 3-6 months post initiation of SV therapy
Mean change in left atrial strain parameters pre- and post-SV therapy
Time frame: At least 3-6 months post initiation of SV therapy
Correlation between therapy-associated changes in left atrial strain parameters and therapy-associated changes in left ventricular ejection fraction and/or serum NT pro-BNP level.
Time frame: At least 3-6 months post initiation of SV therapy
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 13 Apr 2026.
- Individual participant dataSharing planned: Yes. Data can be made available upon reasonable request
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 and Reduced Ejection Fraction, run by Connolly Hospital Blanchardstown at 1 site in Ireland.
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 5 inclusion and 4 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 13 Apr 2026. 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 Ireland. 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?
Correlation between pre-therapy left atrial strain parameters on speckle-tracking echocardiography and therapy-associated changes in left ventricular ejection fraction and/or serum NT-pro BNP. (time frame: At least 3-6 months post initiation of SV therapy). 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 13 Apr 2026; AzTrials last refreshed its copy on 6 Nov 2026.