A trial examining if less fluid administration is better than standard fluid administration in children undergoing kidney transplant
| ISRCTN | ISRCTN21516608 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21516608 |
| IRAS number | 354370 |
| Secondary identifying numbers | NIHR206591, CPMS 69346 |
- Submission date
- 09/07/2025
- Registration date
- 21/07/2025
- Last edited
- 11/08/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Surgery
Plain English summary of protocol
Background and study aims
Kidney transplantation is the treatment of choice for children with established kidney failure. Children having a kidney transplant receive fluid by a drip, both during and after the operation. The best amount of fluid for children with a new transplant is not known. Too little fluid can cause delays in the kidney transplant working, or blood clots in the transplant. Too much fluid can cause breathing difficulties, swelling, high blood pressure, headaches or fits. These problems are important to patients and take up valuable specialist NHS resources. There is a pressing need to work out the best amount of fluid for children having a kidney transplant. We are a group of kidney doctors, surgeons, a psychologist, parents, young people and trial experts working together on the LIMITS research study to answer this question. Our aim is to find out whether children having kidney transplants should have a limited amount of fluid given according to their body size, or the larger volumes of fluid that are usually given. Following input from parents and young people a key aim of this research is helping children spend more time at home after transplant.
This study will help to work out the best amount of fluid for children after kidney transplant. This could speed up children’s recovery, improve their experience of transplant and free up specialist NHS resources. It therefore has the potential to change clinical practice and importantly improve the treatment and outcomes of children receiving kidney transplants in the UK. We will publish the results in a widely read medical journal and present them at conferences and on the study website.
Who can participate?
Any child or young person who is receiving a kidney-only transplant from either a living or deceased donor in a participating UK centre may participate. The child or young person must be under the age of 18 years at the time of kidney transplantation.
What does the study involve?
The study will compare recovery in children having different amounts of fluid after kidney transplant. Some children will receive the large amounts that doctors usually give. For others, we will limit the amount of fluid given according to their body size. An independent process called randomisation will decide which fluid amount each child receives. The fluid will be given through a vein (intravenously), by mouth (enterally) or by the child’s usual route. All transplant recipients are given intravenous fluids or enteral fluids during their admission, so this is not an additional burden for trial participants. There will be no study specific blood samples and no extra study visits beyond routine clinical follow up. Blood tests will be done as per standard care with options for mild topical anaesthetics and use of distraction techniques. We will assess children's recovery by the number of days spent at home (rather than in hospital) after transplant. We will work out the impact on health and health service costs from limiting fluid compared to usual practice.
We hope that 140 children from the 10 UK children’s kidney transplant hospitals will take part over 2 years. This number is calculated to ensure that the study is large enough to reach a firm conclusion. Children who agree to join the study will be split into 2 equal groups. Depending on what group the child is in, they will receive either usual amounts of fluid, or a limited amount of fluid tailored to their body size. We will ask children and parents to report their symptoms and experience of their transplant hospital stay.
What are the possible benefits and risks of participating?
Possible benefits:
Research participants may experience less unpleasant symptoms from fluid overload (i.e. less swelling, shortness of breath, headache and fits) and subsequently avoid further intervention to investigate and treat these symptoms which could be uncomfortable or cause psychological distress (i.e. additional medications, blood transfusion, oxygen, additional investigations such as chest x-ray). They may potentially go home earlier after kidney transplant so spend less time in hospital.
Possible Risks:
There are few risks to taking part in this trial, above the risk of kidney transplantation itself. The key risks of liberal fluid administration (current majority practice) are related to fluid overload and are:
• high blood pressure which can lead to headaches and seizures
• fluid on the lungs (pulmonary oedema) which can lead to difficulty breathing
• electrolyte disturbance which can lead to fits (seizures)
• increased blood transfusions
• unexpected intensive care or high dependency unit admission
Some clinicians expressed concern about delayed transplant function and/or thrombosis with a capped fluid approach but this risk is not evidenced-based. Observational data in paediatric kidney transplant recipients <20kg have shown favourable outcomes with less liberal intra-operative fluid volume administration. There is no evidence base for the current liberal use of fluid.
These risks will be mitigated by frequent monitoring of clinical observations. If identified, prompt investigation and treatment will be commenced. This practice will be followed in both arms of the clinical trial. In summary, the risks of participating in the study are not felt to be greater than those of standard clinical care.
Where is the study run from?
Great Ormond Street Hospital for Children NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
January 2025 to December 2027
Who is funding the study?
National Institute for Health and Care Research (UK)
Who is the main contact?
Dr Wesley Hayes, chief investigator, Wesley.Hayes@kispi.uzh.ch
Dr Nuala Calder, clinical research fellow, n.calder@ucl.ac.uk
Dr Fotini Kaloyirou, trial manager, fotini.kaloyirou@nhsbt.nhs.uk
Contact information
Scientific, Principal Investigator
Great Ormond Street Hospital
London
WC1N 1EH
United Kingdom
| Phone | +41 78 326 1236 |
|---|---|
| Wesley.Hayes@kispi.uzh.ch |
Public
NHSBT CTU
Long Road
Cambridge
CB2 0PT
United Kingdom
| Phone | +44 7385388072 |
|---|---|
| fotini.kaloyirou@nhsbt.nhs.uk |
Scientific
Bristol Royal Hospital for Children, Paediatric Nephrology Department, Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom
| Phone | +44 7385388072 |
|---|---|
| n.calder@ucl.ac.uk |
Study information
| Study design | A pragmatic multicentre open label randomized controlled trial with internal pilot phase and integrated economic evaluation |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment, Efficacy |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A randomised multiple centre trial of conservative versus liberal fluid administration for children receiving a kidney transplant |
| Study acronym | LIMITS |
| Study objectives | A relative limitation of fluid volume administered to children receiving kidney transplant is superior to usual liberal fluid volume administration in terms of days at home to 30 days after transplant. |
| Ethics approval(s) |
Submitted 19/06/2025, Cambridge South REC (The Old Chapel Royal Standard Place, Nottingham, NG1 6FS, United Kingdom; +44 207 104 8084; cambridgesouth.rec@hra.nhs.uk), ref: 25/EE/0161 |
| Health condition(s) or problem(s) studied | Fluid management in paediatric kidney transplantation |
| Intervention | Summary of treatment in each group: - Intervention: Fluid volume administration capped at maximum 150ml/m²/hour for no longer than 18 hours following transplant, reduced to a fixed daily target of maximum 1.5 litres/m²/day thereafter. No specific urine output will be targeted. No diuretics to be administered throughout. - Comparator: Target urine output >2ml/kg/hour. Fluid administered to replace urine output + insensible losses for at least 48 hours. Diuretics per the clinical team’s usual practice. Follow up period: Follow up data up will be collected up to 3 months post-transplant. Randomisation: Eligible patients who have consented to participate in LIMITS will be randomised via an interactive web response system, provided by Sealed Envelope. Participants will be randomised in a 1:1 ratio, to the intervention and comparator groups. The randomisation will be stratified by transplant centre and donor type (deceased vs. living donation). Randomisation will further be balanced within blocks of varying, undisclosed sizes. |
| Intervention type | Other |
| Primary outcome measure | Mean days at home in the first 30 days after kidney transplant measured using patient records |
| Secondary outcome measures | 1. Patient-reported experience of transplant hospital stay (from admission to discharge) 2. Proportion of participants with systemic hypertension (systolic blood pressure above the 95th centile for age and height on 2 consecutive days) within 7 days after transplant 3. Proportion of participants with pulmonary oedema on chest x-ray within 7 days after transplant 4. Proportion of participants with severe acute hyponatraemia (plasma sodium concentration <130mmol/l) within 7 days after transplant 5. Proportion of participants receiving a red blood cells within 7 days after transplant 6. Proportion of participants with transplant thrombosis in the post-operative period leading to graft failure within the first 30 days 7. Proportion of participants with delayed transplant function (dialysis within the first 7 days after transplant) 8. Mean transplant function measured by estimated glomerular filtration rate at 3 months post-transplant 9. Cost-effectiveness analysis: kidney-related costs within the study period (all costs incurred and implications for patient health within the study.) |
| Overall study start date | 01/01/2025 |
| Completion date | 30/12/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 0 Months |
| Upper age limit | 18 Years |
| Sex | Both |
| Target number of participants | 140 |
| Key inclusion criteria | 1. Children under 18 years of age at the time of transplantation with valid informed consent 2. Children receiving a kidney only transplant from either a living or deceased donor, in a participating UK centre |
| Key exclusion criteria | Multi-organ transplant recipients |
| Date of first enrolment | 01/06/2025 |
| Date of final enrolment | 31/05/2027 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
Study participating centres
London
WC1N 3JH
United Kingdom
London
SE1 7EH
United Kingdom
Upper Maudlin Street
St Michael's Hill
Bristol
BS2 8BJ
United Kingdom
St. Chads Tunnel
Birmingham
B4 6NH
United Kingdom
Manchester
M13 9WL
United Kingdom
Leeds General Infirmary
Leeds
LS1 3EX
United Kingdom
Glasgow
G51 4TF
United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom
Derby Road
Lenton
Nottingham
NG7 2UH
United Kingdom
Belfast
BT12 6BA
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Eaton Road
West Derby
Liverpool
L12 2AP
United Kingdom
Sponsor information
Hospital/treatment centre
Great Ormond Street
London
WC1N 3JH
England
United Kingdom
| Phone | +44 (0)207 905 2271 |
|---|---|
| vanshree.patel@gosh.nhs.uk | |
| Website | http://www.gosh.nhs.uk/ |
"ROR" |
https://ror.org/03zydm450 |
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 | 30/12/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | All research teams and PPI members involved in the study will be invited to a close out meeting to discuss the findings of the study. Study findings will be presented to academic and non-academic groups. The PPI group will play an important part in disseminating the study findings into the public domain. Dissemination to non-academic audiences including service users, commissioners, clinicians and service providers will be facilitated through the use of existing networks e.g. email lists, social media. Open access, peer reviewed academic outputs and research reports together with associated summaries and key findings will be produced for funders, policy makers and NHS audiences and held on the study website. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from NHSBT Clinical Trials Unit (ctu@nhsbt.nhs.uk). The type of data: fully anonymised analysis dataset. When the data will become available and for how long: 9 months after publication and ending 5 years following article publication. By what access criteria data will be shared including with whom: Data will be shared with investigators whose use of the data has been assessed and approved by an NHSBT review committee and the Sponsor as a methodologically sound proposal. A full Data Sharing Request form will be required. For what types of analyses, and by what mechanism: to be agreed before data is shared Whether consent from participants was obtained: Data of participants who have not agreed to the use of their data for future research, will be removed from the dataset. Comments on data anonymisation: data will be anonymised prior to sharing. Any ethical or legal restrictions: none. Any other comments: a contract is mandatory before any data is shared with a third party. |
Editorial Notes
11/08/2025: Internal review.
09/07/2025: Trial's existence confirmed by Great Ormond Street Hospital for Children NHS Foundation Trust.
