A clinical trial looking at maintaining hydration at the end of life
| ISRCTN | ISRCTN65858561 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN65858561 |
| IRAS number | 313640 |
| Secondary identifying numbers | HTA NIHR131687, IRAS 313640 |
- Submission date
- 10/09/2021
- Registration date
- 14/09/2021
- Last edited
- 05/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English Summary
Background and study aims
The use of clinically-assisted hydration (CAH) in the last days of life is very variable and controversial because there is no good quality research to show whether it improves (or worsens) end-of-life care. In some cases there is a clear indication to start/continue CAH, whilst in other cases there is a clear indication to not start/discontinue CAH. However, in most cases there is no indication one way or another.
The research team has just completed a feasibility (provisional) study, which included 200 cancer patients from hospices/hospitals in England and Wales. The results suggest that CAH may delay the onset of delirium, but that CAH can cause side effects in some patients (e.g. fluid retention). A larger study is needed to properly evaluate the role of CAH. Recently, the Palliative and end-of-life care Priority Setting Partnership (involving patients, carers, patient support groups, members of the general public, and healthcare professionals) concluded that CAH was an important area for research.
The aim is to assess whether giving cancer patients in the last days of life clinically-assisted hydration (or CAH) is effective at preventing them from experiencing “terminal agitation”. This is a distressing form of delirium that often occurs at end-of-life causing restlessness, anxiety and confusion in the patient, and which is very upsetting for family members. We will also explore if CAH affects other end-of-life symptoms (e.g. shortness of breath), length of survival and costs.
Who can participate?
Adults aged over 18 years with a life expectancy of less than 1 week
What does the study involve?
The study will be a so-called cluster randomised trial, which means that hospices/hospitals ('clusters') will be randomly allocated to one of two standard (usual) interventions. Intervention A involves supporting the patient to drink, regular mouth care, and management of pain and other symptoms. Intervention B involves supporting the patient to drink, regular mouth care, management of pain and other symptoms, and CAH. All eligible patients within each hospice/hospital will receive the same intervention (if appropriate). 80 hospices/hospitals in the United Kingdom and 1,600 cancer patients in the last week of life will take part in the study. Patients will be given fluids either into a vein or into the tissues under the skin. The amount of fluid given will be based on the patient’s weight, and the decision to continue/discontinue the fluids will be made by doctors.
Patients will be assessed for end-of-life problems every 4 hours by nursing staff, and data will be collected on the presence of problems, use of medication (to treat problems), and side effects of CAH.
What are the possible benefits and risks of participating?
None
Where is the study run from?
University of Surrey (UK)
When is the study starting and how long is it expected to run for?
September 2021 to March 2025
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Prof. Andrew Davies
andavies@tcd.ie
Contact information
Scientific
School of Medicine
Trinity College Dublin
152-160 Pearse Street
Dublin
D2
Ireland
 ORCID ID |
0000-0003-4207-4799 |
|---|---|
| Phone | +44 (0)7786260295 |
| andavies@tcd.ie |
Public
University of Surrey
Surrey Clinical Trials Unit
Egerton Road
Guildford
GU2 7XP
United Kingdom
| a.mcclave@surrey.ac.uk |
Public
University of Surrey
Surrey Clinical Trials Unit
Egerton Road
Guildford
GU2 7XP
United Kingdom
| chelseaii@surrey.ac.uk |
Study information
| Study design | Multi-centre cluster randomized trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Cluster randomised trial |
| Study setting(s) | Hospice, Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN65858561_PIS_Arm B_V1.0_27Jul22.pdf |
| Scientific title | A cluster randomised trial of clinically-assisted hydration in patients in the last days of life - CHELsea II |
| Study acronym | CHELsea II |
| Study hypothesis | Clinically-assisted hydration (CAH) in the last days of life reduces the frequency of delirium (and the requirement for sedative medication), as a result of preservation of renal function, and prevention of build-up of drugs and toxins. Furthermore, CAH will prevent death due to dehydration occurring before death due to the underlying disease (or its complications). |
| Ethics approval(s) | 1. Main: Approved 09/08/2022, London - Brighton & Sussex Research Ethics Committee (Health Research Authority, 2 Redman Place, Stratford, London, E20 1JQ, UK; +44 (0)207 104 8202, +44 (0)207 104 8241; brightonandsussex.rec@hra.nhs.uk), ref: 22/LO/0475 2. Scotland: Approved 09/09/2022, Scotland A Research Ethics Committee (South East Scotland Research Ethics, Service, 2nd Floor, Waverley Gate, 24 Waterloo Place, Edinburgh, EH1 3EG, UK; +44 (0)131465 5680; sesres@nhslothian.scot.nhs.uk), ref: 22/SS/0053 |
| Condition | Patients in the last week of life (cancer, non-malignant disease) |
| Intervention | Research sites will be randomised to either “standard intervention A” or “standard intervention B” (see below), and this will become the standard of care at the research site for the duration of this study. The interventions represent the current typical standards of care in the UK. Randomisation will be undertaken 1:1 by cluster, to ensure balance and equal numbers in each intervention group, stratifying by home country (i.e. England, Wales, Scotland or Northern Ireland), and by type of unit (i.e. hospital or hospice). Standard intervention A involves: continuance of oral intake (if appropriate) - includes assistance with drinking as required. regular “mouth care” - mouth care should be performed at least every four hours, and should correspond to the research site’s usual procedures for oral care in the terminal phase. Mouth care should be undertaken by the clinical team (but can involve carers if deemed appropriate). Mouth care should be discontinued/withheld if it causes distress/discomfort to the patient, or is otherwise difficult to undertake. standard management of pain and other end-of-life symptoms/problems - should correspond to the research site’s usual procedures for managing relevant problems in the terminal phase. Standard intervention B involves: continuance of oral intake (if appropriate) - see above. regular mouth care - see above. standard management of pain and other end-of-life symptoms/problems - see above. CAH - see below. The parenteral fluids may be given either intravenously (if an intravenous cannula is present), or subcutaneously (if no intravenous cannula is present). Intravenous fluids must be administered using an infusion pump, and subcutaneous fluids must be administered using gravity (and not using an infusion pump). The type/volume of fluid administered is based upon relevant NICE guidance: the fluid to be given is dextrose saline (4% dextrose, 0.18% sodium chloride), and the volume to be given is dependent on the patient's weight (Table 2). It should be noted that the volume of fluid is based on a figure of 25 ml/kg/day, which is the lower limit for generic patients, and the upper limit (for consideration) in “old” or “frail” patients. Intravenous fluids should be administered according to the research site’s usual procedures. Subcutaneous fluids should be administered according to the following guidelines: Patient’s weight Volume of fluid ≤ 40 kg 1 L 50 kg 1.25 L 60 kg 1.5 L 70 kg 1.75 L ≥ 80 kg 2 L Site of cannula - the preferred cannula sites are the lower lateral abdomen, and the upper lateral chest (rather than the upper arm, or the upper leg). If the cannula needs to be changed, then an alternative site should be used. Type of cannula - the preferred cannula is a 24 g BD Saf-T-Intima cannula. Rationale for changing cannula - the decision to change/re-site a cannula is at the discretion of the clinical team. Minimal (asymptomatic) swelling is expected at the site of the cannula, and is not in itself a reason to discontinue the infusion and/or re-site the cannula. Rate of infusion - the preferred method of infusion is continuous infusion with the drop rate calculated in the usual manner. Rationale for discontinuing the infusion - the decision to discontinue the infusion is at the discretion of the clinical team. Minimal (asymptomatic) swelling is expected at the site of the cannula, and is not in itself a reason to discontinue the infusion. The development of audible upper airways secretions (“death rattle”) is also not in itself an indication to discontinue the infusion, since the development of this problem seems independent of hydration status/use of CAH. Participants will be reviewed at least every four hours by the clinical team, and an assessment made as to whether or not certain symptoms/problems are present, i.e. delirium, audible upper respiratory secretions (“death rattle”), pain, shortness of breath, and nausea and vomiting. The clinical team will also assess patient’s level of sedation every four hours, and document the indication for dispensing all as required and regular medication. The clinical team will complete a study-specific clinical observation document, which will be transcribed by the research team into the study case report form. The maximum duration of the study is 14 days: the end of the study occurs with the death of the patient, the withdrawal of the patient, or the completion of 14 days. The duration of the interventions is the same as the duration of the study, unless the clinical team deem that the relevant intervention should be modified/discontinued. For example, mouth care should be discontinued if it causes distress/discomfort to the patient. Patients that have their treatment modified/discontinued will remain in the study (and their data analysed on an intention to treat basis). |
| Intervention type | Behavioural |
| Primary outcome measure | Number of patients that develop delirium during the study. The Nursing Delirium Screening Scale (Nu-DESC) will be used to diagnose patients with delirium. |
| Secondary outcome measures | Measured throughout the study: 1. The proportion of patients that receive as-required and/or regular medication for delirium (data derived from drug chart). 2. Time to the first dose of medication for delirium (as-required or regular – data derived from drug chart). 3. Modified Richmond Agitation and Sedation Scale (m-RASS) scores during the study (mean score; proportion time with score 0; proportion time with score 0 to -2 – data derived from clinical observation document). 4. The proportion of patients with audible upper airway secretions (“death rattle” – data derived from clinical observation document). 5. The proportion of patients that receive as-required and/or regular medication for audible upper airway secretions (data derived from drug chart). 6. Time to the first dose of medication for audible upper airway secretions (as-required or regular – data derived from drug chart). 7. Proportion patients that experience pain, shortness of breath, and nausea and vomiting (and require medication for these symptoms – data derived from clinical observation document and drug chart). 8. Adverse effects of clinically-assisted hydration (data derived from clinical observation document). 9. Overall survival (data derived from clinical observation document). 10. Health economic analysis (data derived from clinical observation document and drug chart). 11. Carer feedback on end-of-life care and research participation. |
| Overall study start date | 10/09/2021 |
| Overall study end date | 14/03/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1,600 |
| Total final enrolment | 1563 |
| Participant inclusion criteria | 1. Aged ≥18 years 2. Estimated prognosis of ≤1 week 3. Patient unable to maintain sufficient oral fluid intake (i.e. <1l/day). |
| Participant exclusion criteria | 1. Patient is dehydrated (patient eligible for inclusion after correction of dehydration) 2. Patient has a relevant Advance Directive to Refuse Treatment (ADRT) 3. Clinical indication for CAH 4. Clinical contraindication to CAH 5. Contraindication to cannulation 6. Total parenteral nutrition/enteral feeding in situ 7. Patient has had delirium in last 24 h 8. Patient has had audible upper airway secretions in last 24 h 9. Patient likely to be transferred elsewhere for end-of-life care |
| Recruitment start date | 01/10/2022 |
| Recruitment end date | 28/02/2025 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Guildford
GU2 7XX
United Kingdom
GU9 8BL
United Kingdom
Esher
KT10 8NA
United Kingdom
North Chailey
Lewes
BN8 4ED
United Kingdom
Pease Pottage
RH11 9SF
United Kingdom
Worthing
BN12 6NZ
United Kingdom
Bosham
Chichester
PO18 8QB
United Kingdom
Margate
CT9 4AD
United Kingdom
Eastbourne
BN22 9PZ
United Kingdom
Pembury
Tunbridge Wells
TN2 4TA
United Kingdom
St. Marys Road
Beccles
NR34 9NQ
United States Minor Outlying Islands
Canterbury
CT2 8JA
United Kingdom
Eglwys
Swansea
SA6 6N
United Kingdom
Aylesford
Maidstone
ME20 7PU
United Kingdom
St Williams Way
Rochester
ME1 2NU
United Kingdom
Sutton-in-ashfield
NG17 4HJ
United Kingdom
Groby Road
Leicester
LE3 9QE
United Kingdom
Scunthorpe
DN17 2AA
United Kingdom
Derby
DE22 3NE
United Kingdom
Derby Road
Nottingham
NG7 2UH
United Kingdom
Hardwick Lane
Bury St. Edmunds
IP33 2QY
United Kingdom
Shelford Bottom
Cambridge
CB22 3FB
United Kingdom
Unthank Road
Norwich
NR2 2PJ
United Kingdom
Willesborough
Ashford
TN24 0NE
United Kingdom
Wells Avenue
Hartlepool
TS24 9DA
United Kingdom
Middlesbrough
TS5 5NW
United Kingdom
North Shields
NE29 8NH
United Kingdom
Llandudno
LL30 2EN
United Kingdom
Holyhead
LL65 2QA
United Kingdom
Penarth
CF64 3YR
United Kingdom
Cardiff
CF14 2TL
United Kingdom
Ashington
NE63 9JJ
United Kingdom
Durham
DH1 3QF
United Kingdom
Newcastle upon Tyne
NE3 1EE
United Kingdom
Hastingwood
Harlow
CM17 9JX
United Kingdom
Watford
WD17 3PH
United Kingdom
Broomfield
Chelmsford
CM1 7FH
United Kingdom
Broxhill Road
Havering-atte-bower
Romford
RM4 1QH
United Kingdom
Barncroft Close
Highwoods
Colchester
CO4 9JU
United Kingdom
North Finchley
London
N12 8TT
United Kingdom
Higher Bebington
Wirral
CH63 6JE
United Kingdom
Eccleston Park
Prescot
L34 2QT
United Kingdom
Lostock Hall
Preston
PR5 5XU
United Kingdom
Bispham
Blackpool
FY2 0BG
United Kingdom
Edinburgh
EH5 3RW
United Kingdom
Bellahouston Park
Glasgow
G41 5BW
United Kingdom
London
SW4 0RN
United Kingdom
Cheam
Sutton
SM3 9DX
United Kingdom
28 Thornbury Road
Uphill
Weston-super-mare
BS23 4YQ
United Kingdom
Edinburgh
EH10 7DR
United Kingdom
Winsley
Bradford-on-avon
BA15 2LE
United Kingdom
Bishops Hull
Taunton
TA1 5HA
United Kingdom
Dorchester
DT1 2SL
United Kingdom
West End
Southampton
SO30 3JB
United Kingdom
Newport
PO30 2ER
United Kingdom
Romsey Road
Winchester
SO22 5DG
United Kingdom
War Memorial Community Hospital
Andover
SP10 3LB
United Kingdom
Basingstoke
RG24 9NB
United Kingdom
Brentry
Bristol
BS10 6NL
United Kingdom
Church Road
Leckhampton
Cheltenham
GL53 0QJ
United Kingdom
176 Raddlebarn Road
Birmingham
B29 7DA
United Kingdom
4 Compton Road West
Wolverhampton
WV3 9DH
United Kingdom
Whittington
Lichfield
WS14 9LH
United Kingdom
Blurton
Stoke-on-trent
ST3 3NZ
United Kingdom
Stourbridge
DY8 2JR
United Kingdom
Warwick
CV34 6PX
United Kingdom
Hornbeam Park Ave.
Harrogate
HG2 8NA
United Kingdom
Hull
HU8 8DH
United Kingdom
Pontefract
WF8 4BG
United Kingdom
Scarborough
YO12 5RE
United Kingdom
Off Chorley New Road
Bolton
BL1 4QT
United Kingdom
Foundry Hill
Hayle
TR27 4HW
United Kingdom
St Asaph
LL17 0RS
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Keighley Road
Oxenhope
Keighley
BD22 9HJ
United Kingdom
Odstock Road
Salisbury
SP2 8BJ
United Kingdom
Royton
Oldham
OL2 6EU
United Kingdom
London
SE26 6DZ
United Kingdom
Ipswich
IP4 5PD
United Kingdom
Wroughton
Swindon
SN4 9BY
United Kingdom
Downs Road
Sutton
SM2 5PT
United Kingdom
Sponsor information
University/education
Stag Hill
Guildford
GU2 7XX
England
United Kingdom
| Phone | +44 (0)1483689797 |
|---|---|
| ctu@surrey.ac.uk | |
| Website | https://ctu.surrey.ac.uk/ |
"ROR" |
https://ror.org/00ks66431 |
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 | 01/04/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Anonymised raw data will be available to bone-fide academic researchers on request at the end of the study (and for 5 years afterwards) - requests need to be made to the study chief investigator (Prof Andrew Davies - andavies@tcd.ie), and a data sharing agreement will be produced between the study sponsor (University of Surrey) and the researchers' academic institution outlining the conditions of use of the data (including proposed analysis of the data). The participant information sheet will discuss the issue of data sharing. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.0 | 27/07/2022 | 20/10/2022 | No | Yes |
| Participant information sheet | version 1.0 | 27/07/2022 | 20/10/2022 | No | Yes |
| Protocol file | version 1.0 | 27/07/2022 | 21/10/2022 | No | No |
| Protocol file | version 1.2 | 09/09/2022 | 28/10/2022 | No | No |
| Protocol article | 23/11/2022 | 24/11/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 1.5 | 19/02/2025 | 05/03/2025 | No | No |
Additional files
Editorial Notes
05/03/2025: The following changes were made to the study record:
1. Protocol uploaded.
2. The recruitment end date was changed from 01/02/2025 to 28/02/2025.
3. The overall study end date was changed from 30/04/2025 to 14/03/2025.
4. Study website and total final enrolment added.
12/09/2024: The recruitment end date was changed from 30/09/2024 to 01/02/2025.
04/03/2024: The study participating centres Phyliss Tuckwell, Princess Alice Hospice, St Peter & St James Hospice, St Catherine's Hospice, St Barnabas Hospice, St Wilfreds Hospice, Pilgrims Hospice In Thanet, St Wilfred's Hospice, Hospice In the Weald, St Elizabeth’s Hospice, Pilgrims Hospice In East Kent, Ty Olwen, The Heart of Kent Hospice, Wisdom Hospice, John Eastwood Hospice, Loros, Lindsey Lodge, Royal Derby Hospital, Nottingham University Hospitals NHS Trust - Queen's Medical Centre Campus, St Nicholas Hospice, Arthur Rank Hospice Charity, Specialist Palliative Care Services, Pilgrims Hospice at Ashford, Alice House Hospice, Teesside Hospice, North Tyneside Specialist Unit, St Davids Hospice, St David Hospice, Marie Curie Cardiff and Vale Hospice, Velindre Cancer Centre, Wansbeck Specialist Unit, St Cuthberts Hospice, St Oswald’s Hospice, St Clare's Hospice, Peace Hospice, Farleigh Hospice, Saint Francis Hospice Sccs, St. Helena Hospice, North London Hospice, St Johns Hospice (in Wirral), Willowbrook Hospice, St Catherine's Hospice, Trinity Hospice Community, St Columba's Hospice, The Prince and Princess of Wales, Royal Trinity Hospice, St Raphael’s Hospice, Weston Hospicecare, Marie Curie Hospice Edinburgh, Dorothy House Hospice, St Margaret's, Weldmar Hospicecare Trust, Countess Mountbatten Hospice, Earl Mountbatten Hospice, Winchester Hospice, Royal Hampshire County Hospital, Countess of Brecknock Hospice, St Michaels Hospice, St Peters Hospice (brentry), Sue Ryder, Leckhampton, Birmingham St Mary's Hospice, Compton Palliative Care Team, St Giles Hospice, Douglas Macmillan Hospice, The Mary Stevens Hospice, Warwick Myton Hospice, Saint Michael’s Hospice - Harrogate, Dove House Hospice, The Prince of Wales Hospice, Saint Catherine's Hospice - Scarborough, Bolton Hospice, St Julia's Hospice, St Kentigern Hospice, Oxford University Hospitals, University Hospital Southampton NHS Foundation Trust, Sue Ryder Manorlands Hospice, Salisbury NHS Foundation Trust, Dr Kershaws Hospice, St Christophers Hospice, Ipswich Hospital, Prospect Hospice, Royal Marsden Hospital, St Barnabas Hospice, Lindsey Lodge, St Nicholas Hospice, St Oswald’s Hospice, St Clare's Hospice, Weldmar Hospicecare Trust, Birmingham St Mary's Hospice, Dove House Hospice, Bolton Hospice were added.
were added.
06/02/2023: The study setting has been changed from ‘Other’.
24/11/2022: Publication reference added.
28/10/2022: Protocol uploaded (not peer reviewed).
21/10/2022: Protocol uploaded (not peer reviewed).
20/10/2022: The following changes were made to the trial record:
1. Participant information sheets uploaded.
2. Ethics approval details added.
3. Northern Ireland, Scotland and Wales were added as countries of recruitment.
23/06/2022: The following changes have been made:
1. The public title has been changed from "A clinical trial of fluids given in an intravenous drip at the end of life" to "A clinical trial looking at maintaining hydration at the end of life".
2. A public contact was added.
22/06/2022: The trial setting has been changed from "Hospitals" to "Other".
14/09/2021: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).
