Effects of Repletion of Sodium Chloride on Natriuresis, Blood Pressure, and Neurohormonal Activity in Patients With Chronic Heart Failure With Reduced Ejection Fraction

NCT07614295 | Not Yet Recruiting

• 2 other identifiers: KB340/20252024/53/N/NZ5/02590
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a single-center, prospective, randomized, placebo-controlled, double-blind trial conducted at the Institute of Heart Diseases and the Department of Cardiology of Wroclaw Medical University Hospital. It aims to evaluate the effects of three-month oral sodium chloride supplementation (3 g/day, equivalent to 1.2 g of sodium) versus placebo (lactose) in patients with chronic heart failure with reduced ejection fraction (HFrEF) and low serum sodium, who have not reached the maximum recommended doses of guideline-directed medical therapy (GDMT). A total of 30 patients will be enrolled, with 15 randomized to the experimental group receiving sodium chloride and 15 to the control group receiving placebo. Patient selection will involve careful screening, including recent serum sodium measurements, to ensure all inclusion and exclusion criteria are met. Participants will attend bi-weekly visits to assess clinical parameters (medical history, EVEREST heart failure symptoms score, blood pressure, body weight), biochemical markers (serum: morphology, urea, creatinine, sodium, chloride, potassium, NT-proBNP, aldosterone, renin; urine: urea, creatinine, sodium, chloride, potassium), and the safety of supplementation (body weight, serum sodium and chloride, exercise tolerance). Visits will also allow attempts to optimize GDMT doses where clinically feasible, based on objective criteria (e.g., systolic blood pressure \>110 mmHg and/or diastolic blood pressure \>60 mmHg). Capsules containing sodium chloride or placebo will be prepared according to pharmacy standards to ensure intestinal release and maintain blinding. The Primary Investigator will remain blinded to treatment allocation. Follow-up will include both in-person and telephone visits, monitoring clinical status and safety parameters throughout the study period. Sample size was calculated based on previous studies in this field, to achieve a type I error probability of 0.05 and a power of 0.80. At the end of the three-month supplementation, participants will undergo a comprehensive final assessment. Study data will be analyzed statistically to determine the effects of sodium chloride supplementation on natriuresis, blood pressure, neurohormonal activity, and the potential for optimizing GDMT in HFrEF patients with low serum sodium.

Conditions

Chronic Heart Failure With Reduced Ejection Fraction

Keywords

sodium supplementation; sodium chloride; HFrEF; chronic heart failure; neurohormonal activity; aldosterone; renin; blood pressure; natriuresis

Outcome Measures

Primary Outcomes (5)

• Sodium Handling and Urine Dilution Response

  Change in the degree of sodium retention (assessed as FeNa) and urine dilution (defined as urineary creatinine baseline to 3-h post-diuretic concentration) following administration of the patient's current diuretic dose in the sodium chloride supplementation group versus placebo group

  3 months observation - predefined timpoints

• Plasma renin and aldosterone assessment

  Assessment of changes in plasma renin and aldosterone concentrations during the study period in the sodium chloride supplementation group versus the placebo group.

  3 months observation - in predefined timepoints

• Mean blood pressure trajectory

  Mean blood pressure assessment during the study period in the sodium chloride supplementation group versus the placebo group

  3 months observation - in predefined timepoints

• Body weight change assessment (safety measurement)

  Long-term assessment of body weight increase between consecutive timepoints. Discontinuation of supplementation if weight increases by more than 2 kg between consecutive timepoints.

  6 months observation - in predefined timpeoints

• Blood pressure assessment (safety assessment)

  Assessment of blood pressure between consecutive timepoints. Discontinuation of supplementation if mean blood pressure decrease below 80/40 mmHg.

  6 moths observation - in predefined timepoints

Secondary Outcomes (4)

• NT-proBNP change

  3 months - predefined timepoints

• Serum sodium concentration change

  3 months - predefined timepoints

• Congestion status change

  3 months - predefined timepoints

• Possibility of GDMT optimization

  3 months - predefined timepoints

Study Arms (2)

Sodium chloride supplementation group

EXPERIMENTAL

Oral supplementation of sodium chloride

Dietary Supplement: Sodium chloride supplementation

Placebo group

PLACEBO COMPARATOR

Placebo (lactose)administration

Dietary Supplement: Placebo administration

Interventions

Sodium chloride supplementation DIETARY_SUPPLEMENT

Oral supplementation with sodium chloride capsules for three months at a total daily dose of 3 g (equivalent to 1.2 g of sodium). The planned regimen is one 1 g sodium chloride capsule taken three times daily.

Sodium chloride supplementation group

Placebo administration DIETARY_SUPPLEMENT

Three-month oral administration of lactose as a placebo, matching the active treatment in appearance and dosing schedule. The planned regimen is one capsule containing lactose three times daily.

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic heart failure NYHA I-III.
• LVEF ≤40% documented in the echocardiography.
• Stable Heart Failure symptoms:
• Stable symptoms (subjectively declared by the patient) over the past three months.
• No increase in peripheral edema or body weight (declared by the patient).
• Loop diuretic dose equivalent to 80 mg of furosemide or 20 mg of torasemide daily, with no changes in the past three months.
• Age over 18 and under 85 years.
• Male or female.
• Use of guideline-directed medical therapy (GDMT), with each drug group at maximum tolerated doses but no more than half of the maximum dose.
• Systolic blood pressure \<100 mmHg and/or diastolic blood pressure \<60 mmHg.
• Resting heart rate up to 80 bpm.
• Serum sodium concentration \<140 mmol/L, regardless of the cause.

You may not qualify if:

• Hospitalization due to heart failure decompensation within the last three months.
• Primary hypertrophic or restrictive cardiomyopathy, constrictive pericarditis.
• Systemic disease known to be associated with cardiac muscle infiltration.
• Significant valvular disease (moderate or severe stenosis of any valve, moderate or severe aortic or pulmonary regurgitation, severe tricuspid or mitral regurgitation).
• Severe renal impairment (eGFR \<30 mL/min/1.73 m² based on the MDRD formula).
• Stroke or transient ischemic attack (TIA) within the last three months.
• Cardiac resynchronization therapy (CRT), ICD, ablation, or pacemaker implantation (or planned implantation) within the last three months.
• Severe lung disease or "cor pulmonale" or other causes of isolated right ventricular failure not associated with left ventricular dysfunction.
• Severe lung disease with respiratory failure requiring home oxygen therapy.
• Body weight \<40 kg or ≥150 kg.
• Life expectancy \<12 months according to the investigator's assessment
• Pregnancy or breastfeeding.
• Ongoing drug or alcohol abuse.
• Lactose intolerance.

Sponsors & Collaborators

• Wroclaw Medical University: lead

Study Sites (1)

Institute of Heart Diseases, Wroclaw Medical University

Wroclaw, Lower Silesian Voivodeship, 50-536, Poland

Location

Related Publications (4)

• Ezekowitz JA, Colin-Ramirez E, Ross H, Escobedo J, Macdonald P, Troughton R, Saldarriaga C, Alemayehu W, McAlister FA, Arcand J, Atherton J, Doughty R, Gupta M, Howlett J, Jaffer S, Lavoie A, Lund M, Marwick T, McKelvie R, Moe G, Pandey AS, Porepa L, Rajda M, Rheault H, Singh J, Toma M, Virani S, Zieroth S; SODIUM-HF Investigators. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial. Lancet. 2022 Apr 9;399(10333):1391-1400. doi: 10.1016/S0140-6736(22)00369-5. Epub 2022 Apr 2.

  PMID: 35381194 BACKGROUND

• Zhao W, Qin J, Lu G, Wang Y, Qiao L, Li Y. Association between hyponatremia and adverse clinical outcomes of heart failure: current evidence based on a systematic review and meta-analysis. Front Cardiovasc Med. 2023 Dec 22;10:1339203. doi: 10.3389/fcvm.2023.1339203. eCollection 2023.

  PMID: 38204798 BACKGROUND

• Mullens W, Damman K, Dhont S, Banerjee D, Bayes-Genis A, Cannata A, Chioncel O, Cikes M, Ezekowitz J, Flammer AJ, Martens P, Mebazaa A, Mentz RJ, Miro O, Moura B, Nunez J, Ter Maaten JM, Testani J, van Kimmenade R, Verbrugge FH, Metra M, Rosano GMC, Filippatos G. Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC. Eur J Heart Fail. 2024 Apr;26(4):730-741. doi: 10.1002/ejhf.3244. Epub 2024 Apr 12.

  PMID: 38606657 BACKGROUND

• Dauw J, Meekers E, Martens P, Deferm S, Dhont S, Marchal W, Mesotten L, Dupont M, Nijst P, Tang WHW, Janssens SP, Mullens W. Sodium loading in ambulatory patients with heart failure with reduced ejection fraction: Mechanistic insights into sodium handling. Eur J Heart Fail. 2024 Mar;26(3):616-624. doi: 10.1002/ejhf.3131. Epub 2024 Jan 21.

  PMID: 38247136 BACKGROUND

Central Study Contacts

Mateusz Guzik M.G. Guzik, MD

CONTACT

+48 71 733 11 12; m.guzik@umw.edu.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 10, 2026
• First Posted: May 29, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Access Criteria: Access to anonymized IPD and supporting information may be granted for individual request submitted to the Principal Investigator. Data access will be considered in justified cases for research purposes and in accordance with applicable data protection regulations.

Locations

PL (1)