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Trial registered on ANZCTR


Trial ID
ACTRN12613000689774
Ethics application status
Approved
Date submitted
14/06/2013
Date registered
24/06/2013
Date last updated
15/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised double blinded controlled pilot trial investigating the effect dietary nitrate in the treatment of acute decompensated heart failure.
Scientific title
Randomised double blinded controlled pilot trial investigating the effect dietary nitrate in the treatment of acute decompensated heart failure.
Secondary ID [1] 282676 0
NIl
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 289376 0
Condition category
Condition code
Cardiovascular 289710 289710 0 0
Coronary heart disease
Cardiovascular 289711 289711 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The dietary nitrate will be in the form of a commercially available beetroot supplement manufactured from organic beetroot by James White Drinks (UK). It is a 70ml preparation that contains 0.4g of dietary nitrate. The researchers have no financial relationship with James White Drinks.

For this study the investigational product and placebo control will be sourced directly from the manufacturer in the UK.

Study Frequency - 5 days of treatment, once daily for 5 days

Intervention code [1] 287334 0
Treatment: Other
Comparator / control treatment
Placebo

The placebo control is also manufactured by the same company and is a nitrate depleted version and is indistinguishable from the nitrate containing preparation
Control group
Placebo

Outcomes
Primary outcome [1] 289803 0
The primary hypothesis in this study is that dietary nitrate supplementation will improve vascular function in ADHF patients.

Assessment of outcome - improvement in symptoms via KCCQ, Endopat tool to assess vascular function,
Timepoint [1] 289803 0
Day 5
Secondary outcome [1] 303265 0
The secondary end point is overall ‘treatment success’ . This composite parameter has been widely used in HF trials. Outcomes are defined as ‘treatment success’, treatment failure, or no change in the patient’s condition. Success is defined as patient-reported moderate or marked improvement in dyspnoea at 5 days, in the absence of any criterion for failure.
Timepoint [1] 303265 0
Day 5

Eligibility
Key inclusion criteria
Age 18-75 years
Acute decompensated HF requiring hospitalization (at the discretion of the treating physician), reflected by clinical signs or symptoms of peripheral or pulmonary congestion
NYHAC III or IV
And LVEF less than 40% (either previously documented or documented at admission)
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age between 18, and 75
Hypotension (BP less than 90)
inotropic therapy
anticipated need for LVAD or ECMO within 48 hrs
endotracheal intubation/ventilation
cardiac or other solid organ transplantation
STEMI at presentation
suspected sepsis
arrhyhthmia as a primary cause for ADHF
Allergy to Beetroot
Pregnancy

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
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Based upon our data and the above hypothesis, with power 80% and the null hypothesis set for rejection at p less than 0.05 we calculate that we require n equals 13 per group. Based on our previous experience we anticipate a drop-out rate of up to 50% per group due to a variety of factors (eg conversion to inotropic therapy, patient withdrawal, loss to follow up, unplanned discharge) hence we request approval of a total of 40 patients.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
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 postcode(s) [1] 6962 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 287449 0
Hospital
Name [1] 287449 0
Alfred Health
Address [1] 287449 0
Alfred Hospital, Commercial Road, Melbourne, Victoria, 3004
Country [1] 287449 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
Alfred Hospital, Commercial Road, Heart Centre, Melbourne, Victoria, 3004
Country
Australia
Secondary sponsor category [1] 286191 0
None
Name [1] 286191 0
Address [1] 286191 0
Country [1] 286191 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289425 0
Alfred Research & Ethics Committee
Ethics committee address [1] 289425 0
The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Ethics committee country [1] 289425 0
Australia
Date submitted for ethics approval [1] 289425 0
05/06/2013
Approval date [1] 289425 0
24/07/2013
Ethics approval number [1] 289425 0
194/13

Summary
Brief summary
The trial will invite patients at the Alfred Hospital, Melbourne, Victoria presenting with acute decompensated heart failure to participate in a study of a dietary supplement (Beetroot extract - Dietary Nitrate) within 48 hours of their hospital admission.
Heart failure is a condition where the heart fails to provide enough blood pumping power for the needs of normal body function. At times the condition may worsen significantly leading to fluid retention, low blood pressure, kidney failure and breathlessness, which usually each requires hospitalization. Currently there are limited treatment options available for these patients and there is a high risk of further hospitalization or death in subsequent months after the patient’s admission to hospital.
In this study we propose to study the effects of dietary nitrate in th patients described above. There is a growing body of evidence that dietary nitrate in the form of concentrated beetroot supplementation has beneficial cardiovascular effects including lowering blood pressure and enhances exercise performance during sub-maximal exercise. Forty patients will be invited to participate in the trial. After obtaining informed consent, twenty patients will be randomly assigned to treatment with oral Dietary Nitrate (70ml concentrated beetroot juice, manufactured by James White UK) or nitrate depleted placebo once daily for five days. This is in addition to any other medication prescribed by their treating doctor.
At enrolment the patients will be educated and counselled about the trial and the intervention medication. Various parameters will be monitored on a daily basis, including objective and subjective symptom review, observations, blood vessel function, weight, kidney function, and medication requirement. Blood samples will also be taken and stored for analysis. We will contact the patient by telephone after 30 days to ask about their health.
The primary objective of the trial is to see whether the administration of dietary nitrate will improve blood vessel function and overall treatment outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40782 0
Prof David Kaye
Address 40782 0
The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Country 40782 0
Australia
Phone 40782 0
+61 3 9076 3263
Fax 40782 0
Email 40782 0
david.kaye@bakeridi.edu.au
Contact person for public queries
Name 40783 0
Dr Joshua Martin
Address 40783 0
The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Country 40783 0
Australia
Phone 40783 0
+61 3 9076 2948
Fax 40783 0
Email 40783 0
j.martin@alfred.org.au
Contact person for scientific queries
Name 40784 0
Dr Joshua Martin
Address 40784 0
The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Country 40784 0
Australia
Phone 40784 0
+61 3 9076 2948
Fax 40784 0
Email 40784 0
j.martin@alfred.org.au