None listed
Conditions
Brief summary
Acute decompensated heart failure (ADHF) is the most frequent reason for hospital admission in Australia, requiring improved treatment strategies. Inorganic sodium nitrate (NaNO3) is an indirect dietary means of delivering nitric oxide (NO), which is deficient in ADHF. It is proposed that NaNO3 will improve circulation via vasodilation, without significant hypotension, whilst improving renal blood flow and preserving renal filtration, in ADHF. The aim of this pilot is to evaluate the feasibility and effectiveness of sodium nitrate (NaNO3 8.4mmol administered in 12- hour intervals) over 48 hours as a treatment for ADHF, correlating systemic levels of NO precursors (Nitrate and Nitrite), with measures of cardiovascular and renal function, in 40 patients. We propose a single centre randomized, double-blind, placebo controlled trial, specifically testing the primary hypothesis that supplemental NaNO3 will result in increased systemic nitrate (NO3-) and nitrite (NO2-) levels, in parallel with improved vasorelaxation, as assessed by systemic vascular resistance index (SVRI). Additional surrogate measures relevant to the known pathophysiology of ADHF will be obtained in order to assess clinical effect on dyspnoea, diuretic efficiency and renal function. The results of this novel strategy will be of significant interest to the heart failure community and may help inform a future, larger study.
Interventions
The intervention in this study is inorganic sodium nitrate which is commonly used as a food preservative: E251. 5 doses of 8.4mmol sodium nitrate will be given via oral tablets in 12 hour intervals. Doses will therefore be given at: 0, 12, 24, 36 and 48 hours. The duration of treatment is 48 hours. Doses will be given on the ward as prescribed on the medication chart. Nursing staff will sign against an administered dose and document/report any omission of dose and/or possible adverse effects exp
The intervention in this study is inorganic sodium nitrate which is commonly used as a food preservative: E251. 5 doses of 8.4mmol sodium nitrate will be given via oral tablets in 12 hour intervals. Doses will therefore be given at: 0, 12, 24, 36 and 48 hours. The duration of treatment is 48 hours. Doses will be given on the ward as prescribed on the medication chart. Nursing staff will sign against an administered dose and document/report any omission of dose and/or possible adverse effects experienced. Nursing staff will be briefed prior to the commencement of the study. A logbook of study drug/placebo will be kept on the ward alongside coded and labelled bottles of pre-prepared courses of study drug/placebo.
Sponsors
Western Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients presenting to the emergency department within the previous 24 hours, with a provisonal diagnosis with ADHF. Diagnosis is based on at least one of: dyspnoea, orthopnoea or oedema, and one sign of: chest crackles, peripheral oedema or ascites, and/or radiological confirmation of pulmonary vascular congestion on chest radiography. BNP and the boston criteria will also be used to refute and affirm true heart failure status.
Exclusion criteria
Patients will be excluded if they have a pre-existing need for inotrope therapy; an eGFR <20 mL/min/1.73m2 or on renal replacement therapy (i.e. dialysis); a baseline systolic blood pressure of < 110mmHg; relevant concomitant condition [haemoglobin of less than 10.0 gm/dL, critical aortic stenosis, isolated severe right sided heart failure, respiratory failure, cirrhosis of the liver (Child Pugh class C), advanced malignancy or advanced dementia]; women of child-bearing potential or nursing mothers, recent Sildenafil use (<24 hours on specific enquiry) or a history of Glucose-6-phosphate deficiency elicited on history or medical record search.
Outcome results
None listed