Plain English Summary
Background and study aims
Chronic Kidney Disease (CKD) affects around 10% of the population. Cardiovascular disease (CVD) is a major cause of morbidity (the relative occurrence of disease) and death in CKD, although this is of a different phenotype (composition) from the general CVD population. Currently, few therapies have proved effective in modifying the increased CVD risk or the rate of renal decline in CKD. There are accumulating data that aldosterone receptor antagonists (ARAs) may offer cardio-protection and delay renal impairment in patients with the cardiovascular phenotype in CKD. The use of an aldosterone receptor blocker in CKD has therefore been increasingly advocated. The aim of the trial is to determine the effects of an ARA on renal and CVD outcomes.
Who can participate?
Six NIHR School for Primary Care Research departments will recruit approximately 120 GP practices which in turn will aim to recruit approximately 2616 men and women who meet the criteria for a diagnosis of CKD stage 3b (ascertained from their last 2 blood tests); the participants also need to meet full trial inclusion criteria. Any potential participant who declines to take part in the trial will be asked if they might be willing to consent instead to review of their medical records for comparative data.
What does the study involve?
Participants will be seen over a period of 3 years. They will be randomly allocated (by a computer programme) to one of two groups of the trial, either a) to receive routine care only, or b) to receive the aldosterone receptor antagonist Spironolactone (25mg daily dose) on top of routine care. After their initial visit and random allocation to one of the two groups, the follow-up schedule of visits will be at weeks 1, 2, 4, 12, 26 and then at intervals of once every 13 weeks until the end of their participation at 156 weeks.
The trial measurements will vary according to the schedule, but will consist of a combination of:
- blood pressure measurement
- blood tests
- side-effect monitoring
- drug monitoring diary card completion
- home blood pressures diary card completion
A subgroup of participants will take part in some additional procedures at intervals:
- 24-hour ambulatory blood pressure measurements
- pulse wave velocity and other arterial wall measurements
What are the possible benefits and risks of participating?
The group receiving Spironolactone potentially may derive protection against further kidney damage and heart disease. However, this will not be known until after trial completion. The group not receiving Spironolactone will receive no potential additional benefit on top of routine care, but do have the knowledge that their contribution to research helps towards the development of better treatments for people suffering from chronic kidney disease.
The group not receiving trial medication will continue to receive routine care from their GP and therefore will be at no further risk by taking part in the trial.
As will all medications, there are potential side-effects from taking Spironolactone, but it is a medication that has been used for various conditions for many years and is considered safe to take for people with no sensitivity to it. Participants are closely monitored during the trial for any side-effects. The main safety concern would be an increased level of potassium in the blood (previous research has shown approximately 2 in 100 people may develop high potassium), therefore frequent blood samples are taken in the early part of the trial to check the level.
Where is the study run from?
The University of Oxford Department of Primary Care Health Sciences, Clinical Trials Unit has set up the trial.
Collaborating investigators are based in the following Universities/cities: Birmingham, Bristol, Derby, Manchester, Nottingham, Southampton.
When is the study starting and how long is it expected to run for?
It is anticipated that recruitment will begin in mid-2013. Participants will be enrolled for a period of 3 years. However, participants will also be flagged for long term follow-up of mortality, initially at 5 years.
Who is funding the study?
The National Institute for Health Research School for Primary Care Research.
Who is the main contact?
Chief Investigator: Professor Richard Hobbs
Trial Manager: Dr Ben Thompson
Dr Ben Thompson
Department of Primary Health Care
23-38 Hythe Bridge Street
Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D) Trial: a prospective randomised open blinded endpoint trial to determine the effect of aldosterone receptor antagonism on mortality and cardiovascular outcomes in patients with stage 3b chronic kidney disease
BARACK D is a prospective randomised open blinded endpoint trial (PROBE) of eligible patients from 120 practices recruited by 6 NIHR School for Primary Care Research departments. Patients identified by their GPs with a diagnosis of Chronic Kidney Disease (CKD) stage 3b will be invited to participate in the full trial and those declining will be asked for written consent to review their records only, for comparative data.
The trial aims to determine whether the addition of an aldosterone receptor antagonist in patients with moderate Chronic Kidney Disease (CKD Stage 3b):
reduces onset, or progression of, cardiovascular disease
improves measures of vascular resistance
improves left ventricular function
reduces decline in renal function, based upon measurement of estimated glomerular filtration rate (eGFR) on MDRD criteria.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=14611
NRES Committee South Central Oxford B (13/SC/0114), 09/04/2013, ref: 13/SC/0114
Prospective randomised open blinded endpoint trial; Interventional; Design type: Screening, Treatment
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Topic: Primary Care Research Network for England; Disease: Chronic Kidney Disease
Once-a-day treatment, This is provided on top of routine care.
The daily treatment is the licenced drug Spironolactone 25g (aldosterone receptor antagonist).
This is a candidate for potential cardio-protection in CKD and delay of renal impairment in patients with the cardiovascular disease phenotype in CKD.
Routine Care: Routine care alone
Primary outcome measures
Effect of aldosterone receptor antagonism on mortality and cardiovascular outcomes; Timepoint(s): Baseline assessment (visit 0) and randomisation.
Subsequent assessments at weeks: 1, 2, 4, 12, 26
Secondary outcome measures
Measures of cardiovascular haemodynamics
1. Change in carotid-femoral pulse wave velocity from baseline to final visit intensively phenotyped group.
2. Change in blood pressure annually and at final visit
3. Rates of hypotension (<100mgHg systolic or >20mmHg systolic drop on standing)
4. Mean change in ambulatory blood pressure from randomisation to final visited (measured in mmHg) intensively phenotyped group
Left ventricular function
1. Changes in brain natriuretic peptide (BNP)
Decline in renal function
1. Change in albumin:creatinine ratio (ACR)
2. Changes in estimated glomerular filtration rate (eGFR)
Treatment costs and benefits
1. Change in health status on EQ-5D-5L
2. Cost effectiveness analysis
Incidence of TIA
1. Transient Ischaemic Attack as defined by the American Heart Association (2009)
To determine the safety of ARA in patients with stage 3b CKD
1. Rates of adverse events
2. Rates of hyperkalaemia
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Males and females >= 18 years of age
2. Evidence of CKD stage 3b from last 2 recorded blood tests
3. Female patients willing to ensure effective contraception for trial period
4. Able and willing (in recruiting GPs opinion) to comply with all study requirements
Target number of participants
Planned Sample Size: 2616; UK Sample Size: 2616
Participant exclusion criteria
1. Intolerance to Spironolactone or on any prescription medications known to have harmful interactions with Spironolactone.
2. Terminal illness, or other significant medical history deemed unsuitable by GP for this trial.
3. Hyperkalaemia; Type 1 diabetes mellitus; Addisons disease.
4. Chronic heart failure; recent myocardial infarction (within 6 months); documented symptomatic hypotension; baseline systolic BP under 100mmHg.
5. Recent acute kidney injury or admission for renal failure.
6. Alcohol or drug abuse, suspected or known.
7. Female patient who is pregnant, lactating or planning pregnancy during course of the trial.
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Department of Primary Health Care
University of Oxford (UK)
Department of Primary Care Health Sciences
New Radcliffe House
Radcliffe Observatory Quarter Woodstock Road
NIHR (UK) - National School for Primary Care Research; Grant Codes: 118
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24886488
Hill NR, Lasserson D, Thompson B, Perera-Salazar R, Wolstenholme J, Bower P, Blakeman T, Fitzmaurice D, Little P, Feder G, Qureshi N, Taal M, Townend J, Ferro C, McManus R, Hobbs FR, Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D) trial-a multi-centre, prospective, randomised, open, blinded end-point, 36-month study of 2,616 patients within primary care with stage 3b chronic kidney disease to compare the efficacy of spironolactone 25 mg once daily in addition to routine care on mortality and cardiovascular outcomes versus routine care alone: study protocol for a randomized controlled trial., Trials, 2014, 15, 160, doi: 10.1186/1745-6215-15-160.