The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616000951459
Ethics application status
Approved
Date submitted
14/07/2016
Date registered
19/07/2016
Date last updated
19/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility and effects of inorganic nitrate in acute decompensated heart failure
Scientific title
Feasibility and effects of inorganic nitrate in acute decompensated heart failure
Secondary ID [1] 289678 0
None
Universal Trial Number (UTN)
Trial acronym
FINO-ADHF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute decompensated heart failure 299477 0
Condition category
Condition code
Cardiovascular 299457 299457 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 295300 0
Treatment: Drugs
Comparator / control treatment
This is a placebo controlled trial. Participants in the control group will receive microcrystalline cellulose (Avicel 'Registered Trademark') through the same dosing intervals as the intervention group.
Control group
Placebo

Outcomes
Primary outcome [1] 298939 0
A change in systemic nitrite blood plasma levels.

Timepoint [1] 298939 0
At any time point of testing during the treatment phase and immediately following the treatment period. i.e Hours 1, 2, 3, 6, 12, 24, 27, 48, 51. Compared to baseline values obtained at hour zero.
Primary outcome [2] 298940 0
A change in systemic nitrate blood plasma levels.
Timepoint [2] 298940 0
At any time point of testing during the treatment phase and immediately following the treatment period. i.e Hours 1, 2, 3, 6, 24, 27, 48, 51. Compared to baseline values obtained at hour zero.
Secondary outcome [1] 325695 0
Change in arterial stiffness, assessed via SphygmoCor (Registered Trademark); in particular, augmentation pressure (AP) and augmentation index (AI).
Timepoint [1] 325695 0
At points of testing during the treatment phase and immediately following the treatment period. i.e Hours 24, 48. Compared to baseline values obtained at hour zero.
Secondary outcome [2] 325696 0
A change in renal function, as assessed by serial plasma cystatin C levels.
Timepoint [2] 325696 0
At points of testing during the treatment phase and immediately following the treatment period. i.e Hours 24, 48 and pre-discharge. Compared to baseline values obtained at hour zero.
Secondary outcome [3] 325697 0
Dyspnoea relief as per Likert scale.
Timepoint [3] 325697 0
At points of testing during the treatment phase and immediately following the treatment period. i.e Hours 12, 24, 48 and pre-discharge. Compared to baseline values obtained at hour zero.
Secondary outcome [4] 325698 0
Systemic oxygenation as determined by Sp02 assessed by pulse oximetry.
Timepoint [4] 325698 0
At points of testing during the treatment phase and immediately following the treatment period. i.e Hours 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72 and pre-discharge. Compared to baseline values obtained at hour zero.
Secondary outcome [5] 325700 0
Change in serum troponin levels. Using serum samples taken at interval periods.
Timepoint [5] 325700 0
At points of testing during the treatment phase and following the treatment period. i.e Hours 0, 48 and pre-discharge. Compared to baseline values obtained at hour zero.
Secondary outcome [6] 325701 0
A change natriuresis, observable by serial urinary sodium concentrations.
Timepoint [6] 325701 0
At points of testing during the treatment phase and following the treatment period. i.e Hours 0, 48 and pre-discharge. Compared to baseline values obtained at hour zero.
Secondary outcome [7] 325702 0
A change in the incidence of deterioration and complications of treatment, including acute kidney injury, progression to respiratory failure/ventilatory support, hemodynamic compromise, stroke, and death.
This is a composite outcome. Data for this outcome will be collected from hospital medical records at the time of participant discharge from hospital.
Timepoint [7] 325702 0
This outcome will be measured at the time of patient discharge from hospital.
Secondary outcome [8] 325735 0
A change in the measures of cardiac function and cardiopulmonary congestion as assessed by serial point-of-care chest ultrasonography.
This is a composite outcome.
Timepoint [8] 325735 0
At points of testing during the treatment phase and following the treatment period. i.e Hours 0, 6, 48. Compared to baseline values obtained at hour zero.
Secondary outcome [9] 325736 0
A change in blood viscosity assessed through a composite of blood fibrinogen levels
Timepoint [9] 325736 0
At points of testing during the treatment phase and following the treatment period. i.e Hours 0, 3, 24 and 48. Compared to baseline values obtained at hour zero.
Secondary outcome [10] 325754 0
Change in serum B-type natriuretic peptide (BNP) levels. Using serum samples taken at interval periods.
Timepoint [10] 325754 0
At points of testing during the treatment phase and following the treatment period. i.e Hours 0, 48 and pre-discharge. Compared to baseline values obtained at hour zero.
Secondary outcome [11] 325755 0
Change in serum lactate levels. Using serum samples taken at interval periods.
Timepoint [11] 325755 0
At points of testing during the treatment phase and following the treatment period. i.e Hours 0 and 48. Compared to baseline values obtained at hour zero.
Secondary outcome [12] 325756 0
Change in serum ADMA levels. Using serum samples taken at interval periods.
Timepoint [12] 325756 0
At points of testing during the treatment phase and following the treatment period. i.e Hours 0 and 48 . Compared to baseline values obtained at hour zero.
Secondary outcome [13] 325757 0
A change in vasorelaxation as assessed by systemic vascular resistance index using the Physioflow (Registered Trademark) device .

NB:This is a primary outcome.
Timepoint [13] 325757 0
At hours 3, 24, 27, 48 and 51 as compared to baseline measures.
Secondary outcome [14] 325759 0
Proportion of participants exhibiting significant methaemoglobinaemia ( > or = 5%) assessed using blood samples, at 0, 3, 27, 51 hours.
Timepoint [14] 325759 0
At timepoints 0, 3, 27, 51 hours.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
REDCap will be used for electronic data collection and case report forms.
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be presented as mean and standard deviation or median and range, as appropriate to the distribution. Comparisons will utilize t-tests or ANOVA (two way with repeated measures) for normally distributed data. Where appropriate, non-normally distributed data will be logarithmically transformed to achieve a normal distribution, or the Wilcoxon rank sum will be utilized for comparisons.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6166 0
Footscray Hospital - Footscray
Recruitment hospital [2] 6167 0
Sunshine Hospital - St Albans

Funding & Sponsors
Funding source category [1] 294059 0
University
Name [1] 294059 0
University of Melbourne
Address [1] 294059 0
University of Melbourne, Parkville, VIC, 3010
Country [1] 294059 0
Australia
Primary sponsor type
Hospital
Name
Western Health
Address
Western Health Cardiology, Footscray Hospital, Gordon St, 160 Footscray VIC 3011
Country
Australia
Secondary sponsor category [1] 292895 0
None
Name [1] 292895 0
Address [1] 292895 0
Country [1] 292895 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295472 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 295472 0
The Royal Melbourne Hospital - City Campus, 6 East
Grattan Street, Parkville Victoria 3050
Ethics committee country [1] 295472 0
Australia
Date submitted for ethics approval [1] 295472 0
29/03/2016
Approval date [1] 295472 0
15/04/2016
Ethics approval number [1] 295472 0
HREC/15/MH/402

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67418 0
A/Prof Christopher Neil
Address 67418 0
Western Health Cardiology, Footscray Hospital, Gordon St, Footscray VIC
Locked Bag 2, Footscray VIC 3011
Country 67418 0
Australia
Phone 67418 0
+61 3 8345 6666
Fax 67418 0
Email 67418 0
christopher.neil@unimelb.edu.au
Contact person for public queries
Name 67419 0
Dr Michael Seman
Address 67419 0
Western Health Cardiology, Footscray Hospital, Gordon St, Footscray VIC
Locked Bag 2, Footscray VIC 3011
Country 67419 0
Australia
Phone 67419 0
+61 3 8345 6666
Fax 67419 0
Email 67419 0
michael.seman@wh.org.au
Contact person for scientific queries
Name 67420 0
Dr Michael Seman
Address 67420 0
Western Health Cardiology, Footscray Hospital, Gordon St, Footscray VIC
Locked Bag 2, Footscray VIC 3011
Country 67420 0
Australia
Phone 67420 0
+61 3 8345 6666
Fax 67420 0
Email 67420 0
michael.seman@wh.org.au

No information has been provided regarding IPD availability
Summary results
No Results