Acute Heart FailurePhase 4NCT06203236
Natriuresis-Guided Diuretic Therapy in Patients With Acute Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease
A Phase 4 study testing Furosemide 20 MG and diuretic therapy in people with Acute Heart Failure and Chronic Kidney Diseases, run by Assiut University.
Trial summary
To investigate the effectiveness and feasibility of natriuresis-guided diuretic therapy as a personalized approach to managing acute heart failure in patients with underlying chronic kidney disease and its effect on short term outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Heart Failure, Chronic Kidney Diseases
- What is being tested?
- Furosemide 20 MG and diuretic therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- Jan 2024to Nov 2025
- Phase
- Phase 4
- 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
Who may be able to join
- Patients presenting with acute heart failure (AHF) with reduced ejection fraction either De novo or ADHF.
- Patients with chronic kidney disease (CKD) stages 1-4.
- Patients aged 18 years or older.
- Patients accept to participate in the study.
Who cannot join
- Patients with significant stenotic valvular diseases (MS, AS).
- Patients with acute coronary syndrome.
- Patients with acute cardiogenic shock.
- Patients with dyspnea primarily due to non-cardiac cause (significant COPD).
- Patients with severe renal impairment requiring dialysis (GFR < 15 mL/min/1.73 m²).
Trial locations and contacts
No sites are listed yet.
About this study
To investigate the effectiveness and feasibility of natriuresis-guided diuretic therapy as a personalized approach to managing acute heart failure in patients with underlying chronic kidney disease and its effect on short term outcomes.
Read the detailed description
Natriuresis-guided diuretic therapy represents a promising approach in managing the complex and challenging clinical scenario of patients with acute heart failure (AHF) . These patients present a unique set of therapeutic dilemmas as traditional diuretic use to relieve congestion in AHF can potentially exacerbate renal dysfunction in those with preexisting CKD . Natriuresis-guided therapy improve patient centered outcomes by adjusting diuretic treatment based on the measurement of urinary sodium excretion which is feasible and able to improve decongestion in AHF with volume overload .
Patients with both AHF and CKD often experience disrupted fluid dynamics, biochemically, it appears covertly as an abnormality in renal function and when progressive, is manifested by symptom exacerbation and worsening renal impairment during application of therapy to ameliorate such symptoms. The pathways leading to these distinct impairments involve not only hemodynamic deterioration but also neurohormonal, inflammatory, and intrinsic renal mechanisms that produce this syndrome .
Natriuresis-guided diuretic therapy, by focusing on the excretion of sodium in the urine. Natriuresis-guided diuretic therapy assesses sodium excretion in urine, offering a direct way to gauge diuretic effectiveness in managing fluid in heart failure (HF) patients. In HF, neurohormonal activation can cause resistance to loop diuretics, leading to persistent congestion. Urinary sodium (UNa) measurement, recommended by ESC guidelines, helps evaluate diuretic response. Early UNa assessment aligns with observational studies, but controlled trials are ongoing. Traditional metrics like weight loss have limitations. UNa assessment can assist diuretic therapy, but factors like fluid overload severity, timing of assessment, kidney disease, and diuretic type should be considered .
One of the primary advantages of natriuresis-guided therapy is its potential to tailor treatment strategies to individual patient responses. It recognizes that not all patients with AHF and CKD will respond to diuretics in the same way. Natriuretic response measured via the urinary sodium (UNa) concentration in a urine spot sample has gained popularity as a metric used for early assessment of diuretic response. In patients with chronic kidney disease admitted for AHF, assessment of intrinsic renal sodium avidity using a random UNa spot sample provides an opportunity to gain insights into decongestive and diuretic responses to IV diuretic drug administration .
The concept of natriuresis-guided therapy represents a departure from the conventional one-size-fits-all treatment model in acute heart failure (AHF) management. Instead, it aligns with the emerging paradigm of precision medicine, emphasizing that personalized therapeutic decisions should be based on individual patient attributes, notably renal function. This approach holds promise for optimizing diuretic therapy, mitigating the frequency of hospital readmissions, and enhancing the overall quality of life for individuals concurrently experiencing AHF and chronic kidney disease (CKD).
One significant challenge in implementing natriuresis-guided therapy is the need for frequent and accurate measurements of urinary sodium excretion. Urine collection and sodium analysis can be cumbersome and may require specialized equipment .
- Conditions
- Acute Heart Failure, Chronic Kidney Diseases
- Being tested
- Furosemide 20 MG, diuretic therapy
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide 20 MGDrug
Also called Lasix 20 MG
- The median daily total dose of intravenous loop diuretic at the start of treatment will be 20 mg of furosemide.
- Monitoring of urinary sodium excretion (natriuresis) and diuresis will begin 2 hours after treatment initiation.
diuretic therapyOther
diuretic therapy
| Study group | Role | What they receive |
|---|---|---|
| Natriuresis-guided group | Active comparator | Natriuresis-guided therapy group receiving diuretic therapy guided by natriuresis measurements. Receives: Drug: Furosemide 20 MG; Other: diuretic therapy |
| Control group | Active comparator | Patients with matched age and sex as control group receiving diuretic therapy only. Receives: Drug: Furosemide 20 MG; Other: diuretic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean total sodium in urine in both groups.
Measured: 24 hours
Duration of the index hospitalization in both groups.
Measured: 24 hours
Secondary outcomes (4)
All-cause mortality or HF rehospitalization in both groups.
Measured: 90 days
Mean total sodium in urine in both groups.
Measured: 90 days
Incidence of arrythmatic complications as AF, VT and incidence of hypokalemia and hypomagnesaemia in both groups.
Measured: 90 days
Mean total urine output in both groups.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2024
- Study startJan 2024 (estimated)
- Primary completionMar 2025 (estimated)
- Study completionNov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Acute Heart FailureStudies of the same condition, open and under way.
- More trials run by Assiut 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hala Hisham Mohammed Hasan, Assiut University
- Investigators
- Salah Eldin Sayed Atta, Supervisor, Study chair, Assiut UniversityHeba Mahmoud Abdel-Mohsen El-Naggar, Supervisor, Study director, Assiut UniversityMohamed Abdullah Khalifah, Supervisor, Study director, South Valley University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06203236
- Sponsor's protocol ID
- Natriuresis-Guided Diuretics
- Status last verified
- Jan 2024
- First submitted
- 22 Nov 2023
- Last updated
- 12 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Testani JM, Hanberg JS, Cheng S, Rao V, Onyebeke C, Laur O, Kula A, Chen M, Wilson FP, Darlington A, Bellumkonda L, Jacoby D, Tang WH, Parikh CR. Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure. Circ Heart Fail. 2016 Jan;9(1):e002370. doi: 10.1161/CIRCHEARTFAILURE.115.002370.
PubMed 26721915Deferrari G, Cipriani A, La Porta E. Renal dysfunction in cardiovascular diseases and its consequences. J Nephrol. 2021 Feb;34(1):137-153. doi: 10.1007/s40620-020-00842-w. Epub 2020 Sep 1.
PubMed 32870495Raina R, Nair N, Chakraborty R, Nemer L, Dasgupta R, Varian K. An Update on the Pathophysiology and Treatment of Cardiorenal Syndrome. Cardiol Res. 2020 Apr;11(2):76-88. doi: 10.14740/cr955. Epub 2020 Mar 10.
PubMed 32256914Brown JR, Uber PA, Mehra MR. The progressive cardiorenal syndrome in heart failure: mechanisms and therapeutic insights. Curr Treat Options Cardiovasc Med. 2008 Aug;10(4):342-8. doi: 10.1007/s11936-008-0054-5.
PubMed 18647589Oliva-Damaso N, Nunez J, Soler MJ. Spot Urinary Sodium as a Biomarker of Diuretic Response in Acute Heart Failure. J Am Heart Assoc. 2023 Sep 5;12(17):e030044. doi: 10.1161/JAHA.123.030044. Epub 2023 Aug 23. No abstract available.
PubMed 37609987Martens P, Chen HH, Verbrugge FH, Testani JT, Mullens W, Tang WHW. Assessing intrinsic renal sodium avidity in acute heart failure: implications in predicting and guiding decongestion. Eur J Heart Fail. 2022 Oct;24(10):1978-1987. doi: 10.1002/ejhf.2662. Epub 2022 Sep 6.
PubMed 36054180Meekers E, Mullens W. Spot Urinary Sodium Measurements: the Future Direction of the Treatment and Follow-up of Patients with Heart Failure. Curr Heart Fail Rep. 2023 Feb;20(1):88-100. doi: 10.1007/s11897-023-00591-4. Epub 2023 Feb 21.
PubMed 36807114Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, Coster JE, Nieuwland W, van Veldhuisen DJ, Voors AA, Damman K. Natriuresis-guided therapy in acute heart failure: rationale and design of the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial. Eur J Heart Fail. 2022 Feb;24(2):385-392. doi: 10.1002/ejhf.2385. Epub 2022 Jan 6.
PubMed 34791756Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, Postmus D, Coster JE, Nieuwland W, van Veldhuisen DJ, Voors AA, Damman K. Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial. Nat Med. 2023 Oct;29(10):2625-2632. doi: 10.1038/s41591-023-02532-z. Epub 2023 Aug 28.
PubMed 37640861
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natriuresis-Guided Diuretic Therapy in Patients With Acute Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT06203236
- Acronym / sponsor ID
- Natriuresis-Guided Diuretics
- Conditions
- Acute Heart Failure, Chronic Kidney Diseases
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Jan 2024 (estimated)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 12 Jan 2024 (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.
To investigate the effectiveness and feasibility of natriuresis-guided diuretic therapy as a personalized approach to managing acute heart failure in patients with underlying chronic kidney disease and its effect on short term outcomes.
Detailed description
Natriuresis-guided diuretic therapy represents a promising approach in managing the complex and challenging clinical scenario of patients with acute heart failure (AHF) . These patients present a unique set of therapeutic dilemmas as traditional diuretic use to relieve congestion in AHF can potentially exacerbate renal dysfunction in those with preexisting CKD . Natriuresis-guided therapy improve patient centered outcomes by adjusting diuretic treatment based on the measurement of urinary sodium excretion which is feasible and able to improve decongestion in AHF with volume overload .
Patients with both AHF and CKD often experience disrupted fluid dynamics, biochemically, it appears covertly as an abnormality in renal function and when progressive, is manifested by symptom exacerbation and worsening renal impairment during application of therapy to ameliorate such symptoms. The pathways leading to these distinct impairments involve not only hemodynamic deterioration but also neurohormonal, inflammatory, and intrinsic renal mechanisms that produce this syndrome .
Natriuresis-guided diuretic therapy, by focusing on the excretion of sodium in the urine. Natriuresis-guided diuretic therapy assesses sodium excretion in urine, offering a direct way to gauge diuretic effectiveness in managing fluid in heart failure (HF) patients. In HF, neurohormonal activation can cause resistance to loop diuretics, leading to persistent congestion. Urinary sodium (UNa) measurement, recommended by ESC guidelines, helps evaluate diuretic response. Early UNa assessment aligns with observational studies, but controlled trials are ongoing. Traditional metrics like weight loss have limitations. UNa assessment can assist diuretic therapy, but factors like fluid overload severity, timing of assessment, kidney disease, and diuretic type should be considered .
One of the primary advantages of natriuresis-guided therapy is its potential to tailor treatment strategies to individual patient responses. It recognizes that not all patients with AHF and CKD will respond to diuretics in the same way. Natriuretic response measured via the urinary sodium (UNa) concentration in a urine spot sample has gained popularity as a metric used for early assessment of diuretic response. In patients with chronic kidney disease admitted for AHF, assessment of intrinsic renal sodium avidity using a random UNa spot sample provides an opportunity to gain insights into decongestive and diuretic responses to IV diuretic drug administration .
The concept of natriuresis-guided therapy represents a departure from the conventional one-size-fits-all treatment model in acute heart failure (AHF) management. Instead, it aligns with the emerging paradigm of precision medicine, emphasizing that personalized therapeutic decisions should be based on individual patient attributes, notably renal function. This approach holds promise for optimizing diuretic therapy, mitigating the frequency of hospital readmissions, and enhancing the overall quality of life for individuals concurrently experiencing AHF and chronic kidney disease (CKD).
One significant challenge in implementing natriuresis-guided therapy is the need for frequent and accurate measurements of urinary sodium excretion. Urine collection and sodium analysis can be cumbersome and may require specialized equipment .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Natriuresis-guided group | Active comparator | Drug: Furosemide 20 MG, Other: diuretic therapyNatriuresis-guided therapy group receiving diuretic therapy guided by natriuresis measurements. |
| Control group | Active comparator | Drug: Furosemide 20 MG, Other: diuretic therapyPatients with matched age and sex as control group receiving diuretic therapy only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients presenting with acute heart failure (AHF) with reduced ejection fraction either De novo or ADHF.
- Patients with chronic kidney disease (CKD) stages 1-4.
- Patients aged 18 years or older.
- Patients accept to participate in the study.
Key exclusion criteria (5 listed)
- Patients with significant stenotic valvular diseases (MS, AS).
- Patients with acute coronary syndrome.
- Patients with acute cardiogenic shock.
- Patients with dyspnea primarily due to non-cardiac cause (significant COPD).
- Patients with severe renal impairment requiring dialysis (GFR < 15 mL/min/1.73 m²).
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 |
|---|---|---|
| Furosemide 20 MGAlso: Lasix 20 MG1. The median daily total dose of intravenous loop diuretic at the start of treatment will be 20 mg of furosemide. 2. Monitoring of urinary sodium excretion (natriuresis) and diuresis will begin 2 hours after treatment initiation. | Drug | Control group, Natriuresis-guided group |
| diuretic therapydiuretic therapy | Other | Control group, Natriuresis-guided group |
Primary outcome
Mean total sodium in urine in both groups.
Time frame: 24 hours
Duration of the index hospitalization in both groups.
Time frame: 24 hours
4 secondary outcomes
All-cause mortality or HF rehospitalization in both groups.
Time frame: 90 days
Mean total sodium in urine in both groups.
Time frame: 90 days
Incidence of arrythmatic complications as AF, VT and incidence of hypokalemia and hypomagnesaemia in both groups.
Time frame: 90 days
Mean total urine output in both groups.
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2024.
- Background: PubMed 26721915Testani JM, Hanberg JS, Cheng S, Rao V, Onyebeke C, Laur O, Kula A, Chen M, Wilson FP, Darlington A, Bellumkonda L, Jacoby D, Tang WH, Parikh CR. Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure. Circ Heart Fail. 2016 Jan;9(1):e002370. doi: 10.1161/CIRCHEARTFAILURE.115.002370.
- Background: PubMed 32870495Deferrari G, Cipriani A, La Porta E. Renal dysfunction in cardiovascular diseases and its consequences. J Nephrol. 2021 Feb;34(1):137-153. doi: 10.1007/s40620-020-00842-w. Epub 2020 Sep 1.
- Background: PubMed 32256914Raina R, Nair N, Chakraborty R, Nemer L, Dasgupta R, Varian K. An Update on the Pathophysiology and Treatment of Cardiorenal Syndrome. Cardiol Res. 2020 Apr;11(2):76-88. doi: 10.14740/cr955. Epub 2020 Mar 10.
- Background: PubMed 18647589Brown JR, Uber PA, Mehra MR. The progressive cardiorenal syndrome in heart failure: mechanisms and therapeutic insights. Curr Treat Options Cardiovasc Med. 2008 Aug;10(4):342-8. doi: 10.1007/s11936-008-0054-5.
- Background: PubMed 37609987Oliva-Damaso N, Nunez J, Soler MJ. Spot Urinary Sodium as a Biomarker of Diuretic Response in Acute Heart Failure. J Am Heart Assoc. 2023 Sep 5;12(17):e030044. doi: 10.1161/JAHA.123.030044. Epub 2023 Aug 23. No abstract available.
- Background: PubMed 36054180Martens P, Chen HH, Verbrugge FH, Testani JT, Mullens W, Tang WHW. Assessing intrinsic renal sodium avidity in acute heart failure: implications in predicting and guiding decongestion. Eur J Heart Fail. 2022 Oct;24(10):1978-1987. doi: 10.1002/ejhf.2662. Epub 2022 Sep 6.
- Background: PubMed 36807114Meekers E, Mullens W. Spot Urinary Sodium Measurements: the Future Direction of the Treatment and Follow-up of Patients with Heart Failure. Curr Heart Fail Rep. 2023 Feb;20(1):88-100. doi: 10.1007/s11897-023-00591-4. Epub 2023 Feb 21.
- Background: PubMed 34791756Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, Coster JE, Nieuwland W, van Veldhuisen DJ, Voors AA, Damman K. Natriuresis-guided therapy in acute heart failure: rationale and design of the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial. Eur J Heart Fail. 2022 Feb;24(2):385-392. doi: 10.1002/ejhf.2385. Epub 2022 Jan 6.
- Background: PubMed 37640861Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, Postmus D, Coster JE, Nieuwland W, van Veldhuisen DJ, Voors AA, Damman K. Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial. Nat Med. 2023 Oct;29(10):2625-2632. doi: 10.1038/s41591-023-02532-z. Epub 2023 Aug 28.
- Individual participant dataSharing planned: No
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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.
Salah Eldin Sayed Atta, Supervisor study chair
Assiut University
Heba Mahmoud Abdel-Mohsen El-Naggar, Supervisor study director
Assiut University
Mohamed Abdullah Khalifah, Supervisor study director
South Valley University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Furosemide 20 MG and diuretic therapy in people with Acute Heart Failure and Chronic Kidney Diseases, run by Assiut University.
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: status not confirmed, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hala Hisham Mohammed Hasan, Candidate (+201022337251, doctor.hala.hisham@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean total sodium in urine in both groups. (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06203236, which also lists 9 linked publications.
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 12 Jan 2024.