Condition category
Injury, Occupational Diseases, Poisoning
Date applied
20/12/2019
Date assigned
10/01/2020
Last edited
14/04/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Suspended

Plain English Summary

Background and study aims
In the first few days after a kidney transplant, many children develop dangerous changes in the amount of salt and water in the bloodstream. This is because doctors give very large volumes of artificial fluids into the veins to keep the new kidney working. If the main salt in the blood (sodium) falls too far, serious problems including brain damage and even death can occur. Because of this, blood samples are taken every 2-4 hours for the first day after the transplant operation to check sodium levels and change them if necessary.

This research aims to compare the standard fluid used after the transplant operation with an alternative that may reduce dangerous changes in salt (sodium) levels and help the transplant kidney to work better.

The alternative fluid is called PlasmaLyte. It matches the normal composition of blood more closely than standard fluid. PlasmaLyte is already used in other sick children, including those on intensive care units. Although there are good reasons to believe that PlasmaLyte may be a safer choice of fluid for children after kidney transplant, there is no evidence comparing PlasmaLyte with standard fluid for children.

Who can participate?
Patients aged under 18 years receiving a kidney transplant

What does the study involve?
This research will work out which of the two fluids is better by looking at children’s kidney transplants in the UK, half using standard fluid and half using PlasmaLyte. The choice of fluid will be made randomly by a computer. No additional blood samples will be required. Children who participate in the study will continue to have all the usual care that they would otherwise receive.

What are the possible benefits and risks of participating?
This research has the potential to improve the treatment and outcomes of children and young people receiving kidney transplants. Plasma-Lyte may reduce the risk of developing abnormalities in salt (sodium) levels after a transplant operation. Plasma-Lyte may also help the transplant kidney to work better, but at present we do not know if this will be the case. The PLUTO study will help to find out whether Plasma-Lyte is better than current standard care. There are few risks to taking part in this study (above the risk of kidney transplantation). Abnormal levels of salts and minerals in the bloodstream can be experienced by children and young people receiving any fluid. We do not expect these to be more common with Plasma-Lyte but will monitor all children’s blood levels closely to check for this.

Where is the study run from?
1. NHS Blood and Transplant Clinical Trials Unit, UK
2. Belfast City Hospital, UK
3. Birmingham Women's and Children's NHS Foundation Trust, UK
4. University Hospitals Bristol NHS Foundation Trust, UK
5. Great Ormond Street Hospital, UK
6. Guy's and St Thomas' NHS Foundation Trust, UK
7. Leeds Teaching Hospitals NHS Trust, UK
8. Manchester University NHS Foundation Trust, UK
9. The Newcastle Upon Tyne Hospitals NHS Foundation Trust, UK
10. Nottingham University Hospitals NHS Trust, UK

When is the study starting and how long is it expected to run for?
February 2020 to August 2023

Who is funding the study?
National Institute for Health Research (NIHR), UK

Who is the main contact?
Emma Laing (public)
PLUTO@nhsbt.nhs.uk
Dr Wesley Hayes (scientific)
wesley.hayes@gosh.nhs.uk

Trial website

http://www.pluto-study.co.uk

Contact information

Type

Public

Primary contact

Miss Emma Laing

ORCID ID

Contact details

NHS Blood and Transplant Clinical Trials Unit
Long Road
Cambridge
CB2 0PT
United Kingdom
+44 (0)1223 588091
emma.laing@nhsbt.nhs.uk

Type

Scientific

Additional contact

Dr Wesley Hayes

ORCID ID

Contact details

Great Ormond Street Hospital
London
WC1N 3JH
United Kingdom
+44 (0)7522217511
wesley.hayes@gosh.nhs.uk

Additional identifiers

EudraCT number

2019-003025-22

ClinicalTrials.gov number

Nil known

Protocol/serial number

18IA31; CPMS 43031; IRAS 270431

Study information

Scientific title

PlasmaLyte Usage and assessment of kidney Transplant Outcomes in children: the PLUTO trial

Acronym

PLUTO

Study hypothesis

To determine whether the incidence of abnormal and potentially dangerous plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte-148 compared to intravenous fluid with current standard composition

Ethics approval

Approved 20/12/2019, London Central Research Ethics Committee (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH; +44 (0)207 104 8208; NRESCommittee.London-Central@nhs.net), ref: 19/LO/1866

Study design

Interventional randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Available at http://www.pluto-study.co.uk/#patients

Condition

Prevention of hyponatremia in children undergoing kidney transplant

Intervention

SCREENING
All paediatric patients awaiting kidney transplantation will be screened for participation in PLUTO. Data will be collected on the Patient Log. Also as part of this study, a Qualitative Sub-Study will be undertaken to find out more about patients/families opinions of the screening and consent process. To facilitate this, all patients/families who are given the study information sheet will also be given a short questionnaire to complete (whether or not they decide to participate).
The screening data will be regularly reviewed by the Trial Management Group, as well as feedback from the process evaluation.

RANDOMISATION
Informed consent will take place during the pre-transplant preparation period, which typically takes several months. This will allow adequate time for patients and families to consider participating in the study. Randomisation will take place on the day of the transplant (after study consent is re-confirmed verbally by a member of the clinical or Research Team).
Participants will be randomised using an online randomisation service, called SealedEnvelope, and given a unique Randomisation Number. The treatment allocation will also be provided and communicated to all relevant members of the clinical care team at that site.

TREATMENT
The study treatment is Plasma-Lyte 148 (+/- 5% glucose). This will be compared to standard intravenous fluid therapy. Standard therapy varies across the participating sites, which will be accounted for in the trial analysis. The fluid will be administered as required throughout the operation and for 72 hours afterwards as per routine clinical care.

FOLLOW-UP OF PARTICIPANTS
Patients will be reviewed as per standard clinical care. Data will be collected for the trial (e.g. results of blood tests taken as part of standard clinical care). A symptom assessment will be carried out once daily (for 3 days) for headaches, nausea, vomiting and seizures. A proportion of the follow-up data will be obtained the routinely collected data (on the UK Transplant Registry, which is held by NHS Blood and Transplant). No additional study visits or blood tests outside routine clinical care will be required for the trial.

Intervention type

Drug

Phase

Phase IV

Drug names

Plasma-Lyte 148 & Glucose 5% w/v

Primary outcome measure

Acute hyponatraemia in the first 72 hours post-transplant (defined as plasma sodium concentration < 135mmol/l)

Secondary outcome measures

1. Symptoms of acute hyponatraemia (nausea, vomiting, headache, seizures) within the first 72 hours post-transplant
2. The degree of fluid overload experienced (defined as proportional increase in patient weight between pre-transplant weight and maximum weight in the 72 hours post-transplant weight)
3. Time to discharge from hospital (measured from transplant operation start time (“knife to skin”)), measured in days
4. Transplant kidney function at 1, 3, 7 and 90 days (using creatinine-based univariate Schwartz formula(24) to determine eGFR)
5. Other electrolyte abnormalities within the first 72 hours post-transplantation:
5.1. Hypernatraemia (defined as plasma sodium concentration > 145mmol/l)
5.2. Hyperkalaemia (defined as plasma potassium concentration > 5.5mmol/L)
5.3. Hypokalaemia (defined as plasma potassium concentration < 3.5mmol/L)
5.4 Non anion-gap acidosis (defined as plasma bicarbonate < 20mmol/L and anion gap < 20mmol/L)
5.5. Hyperglycaemia (defined as random blood glucose > 5.5 mmol/L)
5.6. Hypomagnesaemia (defined as plasma magnesium concentration < 0.7 mmol/L)
5.7. Hyperchloraemia (defined as plasma chloride concentration > 107mmol/L)
5.8. Excessive rate of reduction in plasma sodium concentration (defined as >1mmol/L/hour averaged over 6 hours)
5.9. Excessive magnitude of reduction in plasma sodium concentration (defined as > 10mmol/L from pre-transplant level)
6. Maximum and minimum systolic blood pressure (normalised to age and height percentile) sustained on 3 repeated values on each day, for 3 days post-transplant
7. Number of changes in intravenous fluid composition and rationale for change within the first 72 hours post-transplant

Overall trial start date

01/08/2019

Overall trial end date

01/08/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Children expected to be under 18 years of age at the time of transplantation
2. Children undergoing preparation for living or deceased donor kidney only transplantation, or active on the deceased donor transplant waiting list for a kidney only transplant at participating UK paediatric transplant centres either pre-emptively (not currently receiving dialysis) or patients on dialysis

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 144; UK Sample Size: 144

Participant exclusion criteria

1. Multi-organ transplant recipients

Recruitment start date

03/02/2020

Recruitment end date

31/08/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

NHS Blood and Transplant Clinical Trials Unit (lead centre)
Long Road
Cambridge
CB2 0PT
United Kingdom

Trial participating centre

Belfast City Hospital
51 Lisburn Road
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Birmingham Women's and Children's NHS Foundation Trust
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
Trust Headquarters Marlborough Street
Bristol
BS1 3NU
United Kingdom

Trial participating centre

Great Ormond Street Hospital
Great Ormond Street
London
WC1N 3JH
United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
St. James's University Hospital Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Manchester University NHS Foundation Trust
Cobbett House Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Freeman Hospital Freeman Road High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Sponsor information

Organisation

Great Ormond Street Hospital for Children NHS Foundation Trust

Sponsor details

Great Ormond St
London
WC1N 3JH
United Kingdom
+44 (0)207 905 2271
vanshree.patel@gosh.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.gosh.nhs.uk/

Funders

Funder type

Government

Funder name

NIHR Central Commissioning Facility (CCF); Grant Codes: NIHR200512

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute for Health Research (NIHR) (UK)

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 publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

31/07/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

14/04/2020: Due to current public health guidance, recruitment for this study has been paused. 30/12/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR)