Oral Sodium to Preserve Renal EfficiencY in Acute Heart Failure

NCT ID: NCT04334668

Last Updated: 2025-05-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-20
• Study Completion Date: 2026-06-01

Brief Summary

The investigators are proposing a prospective, randomized, double blinded, placebo-controlled single center study evaluating the role of co-administration of oral sodium chloride (NaCl) with intravenous diuretics in patients hospitalized with acute decompensated heart failure. The investigators are approaching this study with the hypothesis that the use of oral sodium chloride leads to improved effective diuresis (as measured by weight loss) and renal function as compared to placebo in patients hospitalized with acute decompensated heart failure undergoing aggressive intravenous diuretic therapy.

Detailed Description

Dietary sodium restriction is a common therapeutic intervention in the management of patients hospitalized with decompensated heart failure. This is despite limited supportive data and inconsistent society guidelines.1-3 Randomized clinical trial data has shown that dietary sodium restriction in patients hospitalized with heart failure was not associated with differences in weight, clinical congestion, time to clinical stability but was associated with increased thirst.4 Numerous studies demonstrate that sodium restriction is associated with increased Renin-Angiotensin-Aldosterone System (RAAS) activation as well as increases in inflammatory markers.5,6 These findings challenge of the role of sodium restriction in hospital management of heart failure and have lead to trials that consider a therapeutic role of providing sodium to patients with acute heart failure for its effect in attenuating neurohormonal activation during aggressive diuresis. A central example is the SMAC-HF study from Italy, which showed that in 1771 patients with acute New York Heart Association (NYHA) class IV heart failure, the addition of hypertonic saline (150ml of 1.4%-4.6% NaCl twice a day in addition to diet liberalization led to statistically significant increased urine output and weight loss in addition to reductions in creatinine, length of stay, mortality and readmissions.7 These findings are controversial but similarly favorable results with the use of hypertonic saline in aiding diuresis have been seen in Japan with improved diuresis with continuous hypertonic saline infusions.8 Despite these results, use of sodium chloride supplementation in acute heart failure remains limited. This may be because the practice challenges ingrained clinical practice, but a more likely reason is that the manner of sodium chloride delivery in these trials (hypertonic saline) is often reserved for the Intensive Care Unit (ICU) setting and central venous access for delivery. While small volumes of hypertonic saline are likely safe to be administered in a non-ICU setting, the results would be more broadly applicable and utilized if the manner of sodium supplementation did not require intensive monitoring or central venous access, ie oral supplementation. Therefore, the purpose of the "Oral Sodium to Preserve Renal EfficiencY in Acute Heart Failure" (OSPREY-AHF) is to evaluate the efficacy and safety of oral sodium chloride supplementation compared to placebo in patients with acute decompensated heart failure. While the investigators are specifically interested in sodium chloride and its hypothesized role in attenuating a neurohormonally mediated diuretic resistance commonly seen in patients requiring high dose diuretic therapy, the investigators also intend that by focusing on oral sodium chloride supplementation the investigators may clarify the role of dietary sodium restriction in hospitalized patients with acute heart failure.

Conditions

Volume Overload

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Oral Sodium Chloride

Subject will be given 2 grams of oral sodium chloride three times daily with meals for approximately 4 days

Group Type: ACTIVE_COMPARATOR

Oral Sodium Chloride

Intervention Type: DIETARY_SUPPLEMENT

Subjects will be randomized to receive 2 grams oral Sodium Chloride three times daily with meals for approximately 4 days

Placebo

Subject will be given a placebo orally three times daily with meals for approximately 4 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Subjects will be randomized to receive a placebo three times daily with meals for approximately 4 days.

Interventions

Oral Sodium Chloride

Subjects will be randomized to receive 2 grams oral Sodium Chloride three times daily with meals for approximately 4 days

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Subjects will be randomized to receive a placebo three times daily with meals for approximately 4 days.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old AND
• Admitted to cardiology floor (non-ICU) with primary diagnosis of decompensated heart failure AND
• NT-proBNP >1000 ng/L AND
• Initiation of continuous furosemide infusion at a rate of 10 mg/hr or higher

Exclusion Criteria

• Serum sodium (Na+) level less than 120 or greater than 145.
• Average Systolic Blood Pressure >180 mmHg or Diastolic Blood Pressure >100 mmHg over past 24 hours.
• Anticipated length of stay less than 72 hours.
• Use of vasopressin antagonist
• Current use of sodium chloride tablets
• Active diagnosis of diabetes insipidus
• Inability to tolerate oral diet or swallow pills
• Presence of malabsorptive gastrointestinal disorder (Crohn's disease, short gut syndrome)
• The use of iodinated radiocontrast material in the past 72 hours or anticipated use of intravenous contrast during the current hospitalization
• Admission with intention to transplant or implant permanent Ventricular Assistive Device
• Use of intravenous inotropes, vasopressors or vasodilators at enrollment
• A baseline estimated glomerular filtration rate <15 mL/min/1.73m² according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at the moment of inclusion
• Use of renal replacement therapy at time of enrollment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Wilson Tang

Principal Investigator, Staff Cardovascular & Metabolic Sciences and Cardiovascular Medicine, The Cleveland Clinic

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

W. H. Wilson Tang, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Robert A Montgomery, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 23747642 (View on PubMed)

Heart Failure Society of America; Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, Katz SD, Klapholz M, Moser DK, Rogers JG, Starling RC, Stevenson WG, Tang WH, Teerlink JR, Walsh MN. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2010 Jun;16(6):e1-194. doi: 10.1016/j.cardfail.2010.04.004.

Reference Type: BACKGROUND

PMID: 20610207 (View on PubMed)

McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012 Jul;33(14):1787-847. doi: 10.1093/eurheartj/ehs104. Epub 2012 May 19. No abstract available.

Reference Type: BACKGROUND

PMID: 22611136 (View on PubMed)

Aliti GB, Rabelo ER, Clausell N, Rohde LE, Biolo A, Beck-da-Silva L. Aggressive fluid and sodium restriction in acute decompensated heart failure: a randomized clinical trial. JAMA Intern Med. 2013 Jun 24;173(12):1058-64. doi: 10.1001/jamainternmed.2013.552.

Reference Type: BACKGROUND

PMID: 23689381 (View on PubMed)

Graudal NA, Hubeck-Graudal T, Jurgens G. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review). Am J Hypertens. 2012 Jan;25(1):1-15. doi: 10.1038/ajh.2011.210. Epub 2011 Nov 9.

Reference Type: BACKGROUND

PMID: 22068710 (View on PubMed)

Parrinello G, Di Pasquale P, Licata G, Torres D, Giammanco M, Fasullo S, Mezzero M, Paterna S. Long-term effects of dietary sodium intake on cytokines and neurohormonal activation in patients with recently compensated congestive heart failure. J Card Fail. 2009 Dec;15(10):864-73. doi: 10.1016/j.cardfail.2009.06.002.

Reference Type: BACKGROUND

PMID: 19944363 (View on PubMed)

Paterna S, Fasullo S, Parrinello G, Cannizzaro S, Basile I, Vitrano G, Terrazzino G, Maringhini G, Ganci F, Scalzo S, Sarullo FM, Cice G, Di Pasquale P. Short-term effects of hypertonic saline solution in acute heart failure and long-term effects of a moderate sodium restriction in patients with compensated heart failure with New York Heart Association class III (Class C) (SMAC-HF Study). Am J Med Sci. 2011 Jul;342(1):27-37. doi: 10.1097/MAJ.0b013e31820f10ad.

Reference Type: BACKGROUND

PMID: 21701268 (View on PubMed)

Okuhara Y, Hirotani S, Naito Y, Nakabo A, Iwasaku T, Eguchi A, Morisawa D, Ando T, Sawada H, Manabe E, Masuyama T. Intravenous salt supplementation with low-dose furosemide for treatment of acute decompensated heart failure. J Card Fail. 2014 May;20(5):295-301. doi: 10.1016/j.cardfail.2014.01.012. Epub 2014 Jan 22.

Reference Type: BACKGROUND

PMID: 24462960 (View on PubMed)

Montgomery RA, Mauch J, Sankar P, Martyn T, Engelman T, Martens P, Faulkenberg K, Menon V, Estep JD, Tang WHW. Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure: A Randomized, Placebo-Controlled, Double-Blind Study. J Card Fail. 2023 Jul;29(7):986-996. doi: 10.1016/j.cardfail.2023.03.018. Epub 2023 Apr 11.

Reference Type: DERIVED

PMID: 37044281 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

20-183

Identifier Type: -

Identifier Source: org_study_id