Natural vitamin D (cholecalciferol) versus standard care in patients receiving dialysis
| ISRCTN | ISRCTN15087616 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15087616 |
| EudraCT/CTIS number | 2015-005003-88 |
| Secondary identifying numbers | SIM15 |
- Submission date
- 18/12/2015
- Registration date
- 30/12/2015
- Last edited
- 09/06/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
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 April 2026
Who is funding the study?
National institute for health research (UK)
Who is the main contact?
Dr Rona Smith
Contact information
Scientific
Simplified Trial Office
Cambridge Clinical Trials Unit
Box 401 Cambridge Biomedical Campus
Cambridge
CB2 0QQ
United Kingdom
Study information
| Study design | Multi-centre open-label blinded endpoint pragmatic interventional randomised registry trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet. |
| Scientific title | Natural vitamin D (cholecalciferol) versus standard care in patients receiving dialysis - The SIMPLIFIED randomised registry trial |
| Study acronym | SIMPLIFIED |
| Study objectives | Cholecalciferol 60,000IU by mouth fortnightly will increase survival in patients receiving long term dialysis when compared with standard care. |
| Ethics approval(s) | Cambridgeshire East Regional Ethics Committee, 10/03/2016, ref: 16/EE/065 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/03/2016 |
| Completion date | 30/04/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 4,200 |
| Key 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) |
| Key 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) |
| Date of first enrolment | 14/12/2016 |
| Date of final enrolment | 31/07/2025 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Cambridge
CB2 0QQ
United Kingdom
Whitechapel
London
E1 1BB
United Kingdom
Bradford
BD9 6RJ
United Kingdom
Doncaster
DN2 5LT
United Kingdom
Newcastle upon Tyne
NE7 7DN
United Kingdom
Glasgow
G4 0ET
United Kingdom
Gloucester
GL1 3NN
United Kingdom
London
SE1 9RT
United Kingdom
Ipswich
IP4 5PD
United Kingdom
Leicester
LE1 5WW
United Kingdom
Manchester
M13 9WL
United Kingdom
Norwich
NR4 7UY
United Kingdom
Sheffield
S5 7AU
United Kingdom
Nottingham
NG5 1PB
United Kingdom
London
NW3 2QG
United Kingdom
Liverpool
L7 8XP
United Kingdom
Shrewsbury
SY3 8XQ
United Kingdom
Brighton
BN2 5BE
United Kingdom
Salford
M6 8HD
United Kingdom
Westcliff-on-Sea
SS0 0RY
United Kingdom
London
SG1 4AB
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Liverpool
L9 7AL
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Broomfield
Chelmsford
CM1 7ET
United Kingdom
London
SE5 9RS
United Kingdom
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom
Tooting
London
SW17 0QT
United Kingdom
Leeds
LS9 7TF
United Kingdom
Harrow
London
HA1 3UJ
United Kingdom
Canterbury
CT1 3NG
United Kingdom
Basildon
SS16 5NL
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
Fulwood
Preston
PR2 9HT
United Kingdom
Exeter
EX2 5DW
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Crownhill
Plymouth
PL6 8DH
United Kingdom
Sponsor information
Hospital/treatment centre
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/03/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| 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 plan | 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | 01/12/2015 | 10/05/2021 | No | No |
Editorial Notes
09/06/2025: The following changes were made to the trial record:
1. The recruitment end date was changed from 13/12/2019 to 31/07/2025.
2. The overall end date was changed from 01/03/2025 to 30/04/2026.
3. The plain English summary was updated to reflect these changes.
10/05/2021: Added link to conference presentation.
23/11/2017: The overall trial end date has been updated from 13/12/2024 to 01/03/2025. The recruitment dates have been updated from 14/12/2016-13/12/2019 to 01/03/2017-01/03/2020. The participant exclusion criteria has been updated. The following sites have been removed as trial participating centres: Hull Royal Infirmary, Hammersmith Hospital and University Hospital Coventry. The following sites have been added: Northwick Park Hospital (Imperial- London), Kent & Canterbury Hospital (East Kent), Basildon and Thurrock University (Essex), Oxford- Churchill Hospital, Royal Preston Hospital (Lancashire), Royal Devon & Exeter (Wonford), Royal Stoke University Hospital and Derriford Hospital (Plymouth). The intention to publish date has been updated from 30/03/2025 to 30/03/2026. Added participant level data sharing plans.
27/10/2017: Internal review.
20/10/2016: The following changes have been made to the record:
1. Leeds Teaching Hospital, Queen Elizabeth Hospital (Birmingham), and Royal Derby Hospital have been removed from the list of trial participating centres and five centres have been added
2. The overall trial end date has been updated from 28/02/2024 to 13/12/2024 and the recruitment dates have been updated from 01/04/2016 - 31/03/2019 to 14/12/2016 - 13/12/2019.
15/04/2016: Ethics approval information added.
