Optimising the cardiovascular system following liver transplantation surgery

ISRCTN	ISRCTN10329248
DOI	https://doi.org/10.1186/ISRCTN10329248
Protocol serial number	N/A
Sponsor	University College London
Funder	National Institute for Health Research

Submission date: 21/03/2016
Registration date: 04/04/2016
Last edited: 19/05/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Cirrhosis is a serious complication of liver disease, which involves widespread scarring of the liver. The damage to the liver caused by cirrhosis means that eventually the liver is unable to fulfil its normal functions, ultimately leading to liver failure. Cirrhosis develops gradually, however the damage to the liver is irreversible, and gets worse over time. When cirrhosis is so advanced that the liver is unable to function, a liver transplant is the only treatment option. Liver transplantation is currently the mainstay of treatment for liver failure and more than 800 liver transplants are performed each year in UK. Although a lifesaving treatment, liver transplantation is linked with a high risk of postoperative complications, and nearly two thirds of patients develop serious complications such as failure of the heart and lungs, loss of kidney function, infection, blood clots, or bleeding. Complications such as these can increase a patient’s length of hospital stay, decrease their quality and length of life and result in failure of the transplanted organ, or even death. Following other types of major surgery goal directed fluid therapy (GDFT) is used in order to determine the amount of intravenous (through a drip) fluid needed by the patient. GDFT has been shown to markedly reduce the occurrence of postoperative complications. It is not known whether this method of treating patients is beneficial or harmful following liver transplantation because the fact that these patients have liver cirrhosis means that their bodies process things differently. The aim of this study is to assess the practicability and safety of GDFT following liver transplantation.

Who can participate?
Adults with liver cirrhosis who have been selected to have a liver transplant

What does the study involve?
Participants are randomly allocated to one of two groups. Participants in the first group receive GDFT for 12 hours after their transplant surgery. This involves using a device to measure the volume of blood ejected by the heart at each beat (stroke volume), which is used to determine whether IV fluid should be given to the patient, according to a commonly used method for surgical patients. Participants in the second group are treated using the standard current management of IV fluids (drips) for the first 12 hours after surgery. Participants in both groups are followed up after six months to find out if the new liver is working properly and there have been any complications after the transplant, as well as their quality of life and length of stay in hospital after the surgery.

What are the possible benefits and risks of participating?
There are no direct benefits for participants taking part in this study. In most studies, goal directed fluid therapy has been shown to be of benefit to patients undergoing surgery. Goal directed fluid therapy has never been evaluated in patients following liver transplantation, and we shall closely assess its safety in this setting. There are no notable risks involved with participating in this study.

Where is the study run from?
Royal Free Hospital (UK)

When is the study starting and how long is it expected to run for?
May 2014 to October 2018

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

Who is the main contact?
Dr Daniel Martin

Contact information

Dr Daniel Martin
Scientific

Critical Care Unit
Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom

ORCID ID	0000-0001-6220-8235

Study information

Primary study design	Interventional
Study design	Single-centre randomised controlled feasibility trial
Secondary study design	Randomised controlled trial
Participant information sheet	ISRCTN10329248_PIS_V2_13Apr16.doc
Scientific title	A feasibility study of Cardiac Output optimisation following Liver Transplantation (COLT trial)
Study acronym	COLT
Study objectives	Managing IV fluid requirements using a cardiac output monitor according to a GDFT protocol following transplantation for liver cirrhosis will be both feasible and safe. In addition, surgical outcomes can be improved in this patient group through the use of GDFT, however, the feasibility of this approach must be thoroughly explored prior to a definitive large-scale trial.
Ethics approval(s)	Bloomsbury Research Ethics Committee, 05/01/2016
Health condition(s) or problem(s) studied	Liver transplantation for liver cirrhosis
Intervention	Participants immediately post liver transplant will be randomised on admission to the intensive care unit to one of two treatment groups for the first 12 hours. Intervention group: Participants undergo goal directed fluid therapy (GDFT) for 12 hours post-operatively. This involves the used of a FloTrac cardiac output monitor (EV1000 Clinical Platform, Edwards Lifesciences, Irvine, USA) to measure stroke volume, which will be used to determine IV fluid administration. The Edwards EV1000 cardiac output monitor is a non-invasive pulse wave contour analysis device that calculates cardiac output and stroke volume. Electronic information from the indwelling arterial catheter that all of these patients have inserted as part of their routine treatment is sent to the EV1000 to calculate cardiac output and stroke volume. Control group: Participants are treated using the standard current management of IV fluids for 12 hours post-operatively. Participants in both study arms are followed up after six months
Intervention type	Device
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	FloTrac cardiac output monitor (EV1000 Clinical Platform, Edwards Lifesciences, Irvine, USA)
Primary outcome measure(s)	Feasibility is determined at the end of the study period as the: 1. Ability to recruit patients at the site: A recruitment rate of greater than 40% of patients fulfilling the criteria for this study will be deemed as successful 2. Rate of withdrawal from GDFT protocol: A withdrawal rate of less than 10% will be deemed as successful 3. Reasons for withdrawal from GDFT protocol: Qualitatively assessed 4. Ability to adhere to the GDFT protocol for the 12 hour intervention period: Less than 10% of patients with a deviation from the protocol will indicate success
Key secondary outcome measure(s)	1. Quality of life is measured using Eq5D pre-transplant, 3 and 6 months 2. Postoperative complications are measured using the Clavien-Dindo Classification of surgical complications at 6 months 3. Hospital length of stay is measured using hospital computer system in days 4. ICU length of stay is measured using using hospital computer system in days 5. Graft (liver) function and survival is measured at 6 months by monitoring postoperative complications specifically related to liver transplantation surgery, occurring within 180 days of liver transplantation, defined as any of the following: 5.1. Two or more episodes of graft rejection (biopsy proven and treated) 5.2. Vascular thrombotic episodes 5.3. Bleeding requiring intervention 5.4. Acute kidney injury requiring renal replacement therapy 5.5. Biliary leak requiring intervention 5.6. Biliary stricture requiring intervention 5.7. Cytomegalovirus, fungal or bacterial infection at any site confirmed by culture 6. Patient survival is measured using hospital information system at 6 months
Completion date	01/10/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	50
Total final enrolment	60
Key inclusion criteria	1. Aged between 18 and 80 years 2. Liver cirrhosis 3. Selected to undergo liver transplantation 4. Competent to give consent
Key exclusion criteria	1. Non-cirrhotic liver disease 2. Pregnancy 3. Age less than 18 years or over 80 years 4. Body weight less than 40 kg 5. Re-transplantation for primary graft non-function 6. Fulminant hepatic failure 7. Emergency surgery 8. Known learning disabilities or previously lacking capacity to consent for themselves 9. Prisoners 10. Patients already enrolled in an interventional study 11. Refusal or inability to consent
Date of first enrolment	01/04/2016
Date of final enrolment	31/08/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Royal Free Hospital

Royal Free London NHS Foundation Trust
Pond Street
Hampstead
London
NW3 2QG
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2020	16/07/2020	Yes	No
Protocol article	protocol	07/03/2018		Yes	No
Abstract results		01/12/2018	19/05/2023	No	No
Participant information sheet	version V2	13/04/2016	02/06/2016	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN10329248_PIS_V2_13Apr16.doc: Uploaded 02/06/2016

Editorial Notes

19/05/2023: Publication reference added.
16/07/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
09/03/2018: Publication reference added.
02/06/2016: Participant information sheet uploaded.