Condition category
Digestive System
Date applied
21/03/2016
Date assigned
04/04/2016
Last edited
02/06/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Daniel Martin

ORCID ID

http://orcid.org/0000-0001-6220-8235

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

A feasibility study of Cardiac Output optimisation following Liver Transplantation (COLT trial)

Acronym

COLT

Study hypothesis

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

Bloomsbury Research Ethics Committee, 05/01/2016

Study design

Single-centre randomised controlled feasibility trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Please see additional files

Condition

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

Drug names

Primary outcome measures

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

Secondary outcome measures

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

Overall trial start date

28/05/2014

Overall trial end date

01/10/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged between 18 and 80 years
2. Liver cirrhosis
3. Selected to undergo liver transplantation
4. Competent to give consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

50

Participant 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

Recruitment start date

01/04/2016

Recruitment end date

31/08/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

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

Sponsor information

Organisation

University College London

Sponsor details

University College London
149 Tottenham Court Road
London
W1T 7DN
United Kingdom
+44 20 3447 5557
rfh.randd@nhs.net

Sponsor type

University/education

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

Publication in a high impact peer-reviewed journal

Intention to publish date

01/10/2019

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

02/06/2016: Participant information sheet uploaded.