Condition category
Urological and Genital Diseases
Date applied
18/12/2015
Date assigned
30/12/2015
Last edited
20/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

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 December 2024

Who is funding the study?
National institute for health research (UK)

Who is the main contact?
Dr Thomas Hiemstra

Trial website

Contact information

Type

Scientific

Primary contact

Dr Thomas Hiemstra

ORCID ID

Contact details

Simplified Trial Office
Cambridge Clinical Trials Unit
Box 401 Cambridge Biomedical Campus
Cambridge
CB2 0QQ
United Kingdom

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 measures

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

13/12/2024

Reason abandoned

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

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

Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom

Trial participating centre

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
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 Coventry
Clifford Bridge Road
Coventry
CV2 2DX
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

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/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.

Intention to publish date

30/03/2025

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.