Plain English Summary
Background and study aims
Vitamin D is essential for good health, because it helps our bodies to absorb calcium from the diet. There is a lot of evidence that having enough vitamin D can help prevent against many diseases, such as heart and blood vessel (cardiovascular) disease, bone diseases and cancer. Although vitamins generally come from the diet, in the case of vitamin D, the majority of people actually get most of it from sunlight. When the sun shines on our skin, a reaction in the body is triggered, causing the body to produce an active form of vitamin D called vitamin D3. Vitamin D deficiency is common patients with end stage renal disease (kidney failure), and is a strong predictor of death from cardiovascular disease, infection and cancer. Almost all kidney failure patients who are treated with dialysis are given pre-activated vitamin D to take, however this approach increases blood calcium concentrations which may be harmful, and even make vitamin D deficiency worse. International treatment guidelines therefore now recommend that kidney patients receive inactive vitamin D (cholecalciferol), since we now know that every organ activates its own vitamin D as required, even in patients with kidney failure. However, this is not currently used in the NHS as it has not yet been tested in a trial. The aim of this study is to test whether taking cholecalciferol supplements increases survival in UK dialysis patients.
Who can participate?
Adults living in the UK with dialysis-requiring end stage renal disease.
What does the study involve?
Participants are randomly allocated to one of two groups. Participants in the first group take Cholecalciferol (60,000IU) capsules by mouth once every fortnight for around five and a half years. Participants in the second group continue to receive normal care and are instructed not to take cholecalciferol containing supplements (no more than 1,000IU) for the 5.5 years study period. At the start of the study and then every six months until the end of the study, participants in both groups are contacted to complete questionnaires in order to find out about their quality of life. Seven years after the start of the study, the participants are looked up on the National Deaths Register so that the survival rate of participants in each group can be calculated.
What are the possible benefits and risks of participating?
There are no direct benefits or risks to participants taking part in this study.
Where is the study run from?
Addenbrooke's Hospital (Cambridge) and 35 other NHS hospitals in the UK.
When is the study starting and how long is it expected to run for?
March 2016 to March 2025
Who is funding the study?
National institute for health research (UK)
Who is the main contact?
Dr Thomas Hiemstra
Trial website
Additional identifiers
EudraCT number
2015-005003-88
ClinicalTrials.gov number
Protocol/serial number
SIM15
Study information
Scientific title
Natural vitamin D (cholecalciferol) versus standard care in patients receiving dialysis - The SIMPLIFIED randomised registry trial
Acronym
SIMPLIFIED
Study hypothesis
Cholecalciferol 60,000IU by mouth fortnightly will increase survival in patients receiving long term dialysis when compared with standard care.
Ethics approval
Cambridgeshire East Regional Ethics Committee, 10/03/2016, ref: 16/EE/065
Study design
Multi-centre open-label blinded endpoint pragmatic interventional randomised registry trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet.
Condition
End stage renal disease
Intervention
Participants are randomly allocated to one of two groups.
Intervention group: Participants will receive oral cholecalciferol 60,000IU fortnightly for the duration of the trial mean follow-up 5.5 years.
Control group: Participants will receive standard care but will not be permitted to receive more than 1,000IU per day of cholecalciferol or ergocalciferol.
For all participants, questionnaire-based follow-up will be performed by phone, mail or electronically at 6 monthly intervals for the duration of the trial. Endpoints (death, hospital admissions, cardiovascular events, cancer, infections, fracture) will be obtained from routinely collected data sources including the national deaths register, hospital episode statistics, the UK renal registry, and the UK and Ireland Association of Cancer Registries. The trial will be event-driven, and will complete once 2,200 deaths have occurred.
Intervention type
Drug
Phase
Phase IV
Drug names
Cholecalciferol
Primary outcome measure
All cause mortality will be determined from the national deaths register at 7 years.
Secondary outcome measures
1. Health-related quality of life is measured using the EQ5D questionnaire , determined at 6-monthly intervals for the duration of the trial
2. Hospitalisation-requiring composite cardiovascular events (defined as CV death, acute coronary syndrome, heart failure or arrhythmia and stroke) is determined from Hospital Episode Statistics, and will be obtained at at least 6-monthly intervals for the duration of the trial
3. Hospitalisation for infection is determined from Hospital Episode Statistics, and will be obtained at at least 6-monthly intervals for the duration of the trial
4. Cancer incidence determined from the UK and Ireland Association of Cancer Registries (UKIACR) database after the end of the trial (after 2,200 deaths have occurred, estimated to be 7 years after enrolment of the first participant)
5. Hospitalisation for fracture is determined from Hospital Episode Statistics, and will be obtained at at least 6-monthly intervals for the duration of the trial
6. Cost-effectiveness of cholecalciferol is determined by calculating life years gained per patient (estimated from mortality data from the National Deaths Register (ONS) and Quality Adjusted Life Years (QALYs) gained (estimated from both ONS mortality data and EQ5D data converted to health state utilities relevant to the UK population) at 7 years
Overall trial start date
01/03/2016
Overall trial end date
01/03/2025
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged 18 years or over
2. Have given written informed consent to participate
3. UK Resident
4. Have dialysis-requiring end stage renal disease (ESRD)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
4,200
Participant exclusion criteria
Current exclusion criteria as of 23/11/2017:
1. Current treatment with high dose (>1,000IU/day) cholecalciferol or ergocalciferol in the last 30 days
2. Persistent hypercalcaemia (>2.62 mmol/l on three separate and sequential occasions without precipitating cause)
3. Life expectancy of less than 6 months
4. Women who are pregnant / planning to become pregnant
5. Hypersensitivity to colecalciferol or any of the excipients
6. Not contributing, or willing to contribute, data to the UK Renal Registry (UKRR)
Previous exclusion criteria:
1. Current treatment with high dose (>1,000IU/day) cholecalciferol
2. Persistent hypercalcaemia (>2.62 mmol/l on three separate and sequential occasions without precipitating cause)
3. Life expectancy of less than 6 months
4. Women who are pregnant / planning to become pregnant
5. Inability to provide informed consent
6. Not contributing, or willing to contribute, data to the UK Renal Registry (UKRR)
Recruitment start date
14/12/2016
Recruitment end date
13/12/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
The Royal London Hospital
Whitechapel Road
Whitechapel
London
E1 1BB
United Kingdom
Trial participating centre
Bradford Hospital
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Trial participating centre
Doncaster Hospital
Thorne Road
Doncaster
DN2 5LT
United Kingdom
Trial participating centre
Freeman Hospital
Freeman Road
Newcastle upon Tyne
NE7 7DN
United Kingdom
Trial participating centre
Glasgow Royal Infirmary
84 Castle Street
Glasgow
G4 0ET
United Kingdom
Trial participating centre
Gloucester Royal Hospital
Great Western Road
Gloucester
GL1 3NN
United Kingdom
Trial participating centre
Guys and St Thomas' Hospital
Westminster Bridge Road
London
SE1 9RT
United Kingdom
Trial participating centre
Ipswich Hospital
Heath Road
Ipswich
IP4 5PD
United Kingdom
Trial participating centre
Leicester Royal infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Trial participating centre
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom
Trial participating centre
Norfolk and Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
Trial participating centre
Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom
Trial participating centre
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom
Trial participating centre
Royal Liverpool Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom
Trial participating centre
Royal Shrewsbury Hospital
Mytton Oak Road
Shrewsbury
SY3 8XQ
United Kingdom
Trial participating centre
Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom
Trial participating centre
Salford Royal Hospital
Stott Lane
Salford
M6 8HD
United Kingdom
Trial participating centre
Southend Hospital
Prittlewell Chase
Westcliff-on-Sea
SS0 0RY
United Kingdom
Trial participating centre
Lister Hospital
Chelsea Bridge Road
London
SG1 4AB
United Kingdom
Trial participating centre
Sunderland Royal Hospital
Kayll Road
Sunderland
SR4 7TP
United Kingdom
Trial participating centre
University Hospital Aintree
Longmoor Lane
Liverpool
L9 7AL
United Kingdom
Trial participating centre
University Hospital Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom
Trial participating centre
Broomfield Hospital
Court Road
Broomfield
Chelmsford
CM1 7ET
United Kingdom
Trial participating centre
Kings College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
Trial participating centre
Southmead Hospital
Dorian Way
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom
Trial participating centre
St George’s Hospital
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Trial participating centre
St James’ University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
Trial participating centre
Northwick Park Hospital (Imperial- London)
Watford Road
Harrow
London
HA1 3UJ
United Kingdom
Trial participating centre
Kent & Canterbury Hospital (East Kent)
Ethelbert Road
Canterbury
CT1 3NG
United Kingdom
Trial participating centre
Basildon and Thurrock University
Nethermayne
Basildon
SS16 5NL
United Kingdom
Trial participating centre
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Trial participating centre
Royal Preston Hospital (Lancashire)
Sharoe Green Lane North
Fulwood
Preston
PR2 9HT
United Kingdom
Trial participating centre
Royal Devon & Exeter (Wonford)
Barrack Road
Exeter
EX2 5DW
United Kingdom
Trial participating centre
Royal Stoke University Hospital
Newcastle Road
Stoke-on-Trent
ST4 6QG
United Kingdom
Trial participating centre
Derriford Hospital
Derriford Road
Crownhill
Plymouth
PL6 8DH
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned dissemination of findings via presentations at national and international meetings, and through publication in peer-reviewed journals. In addition to meetings orientated to nephrology, publication of results at meetings aimed at allied health professionals and general practitioners involved in the care of patients receiving dialysis is also planned.
IPD sharing statement:
Regarding the participant level date set, the majority of data collections are made indirectly via UKRR and NHS DIGITAL and are saved on our secure data hosting server (SDHS- the University of Cambridge). The aggregated (not participant level) data might become available after publication.
Intention to publish date
30/03/2026
Participant level data
Stored in repository
Basic results (scientific)
Publication list