Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000172404
Ethics application status
Approved
Date submitted
8/02/2016
Date registered
11/02/2016
Date last updated
2/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Goal-directed Therap for Patients Undergoing Major Liver Resection
Scientific title
A Prospective Multicentre Randomized Controlled Trial of Standard Compared to Surgery Specific Goal-directed Therapy (GDT) for Patients Undergoing
Major Liver Resection
Secondary ID [1] 288471 0
None
Universal Trial Number (UTN)
U1111-1179-1452
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
liver cancer 297507 0
Condition category
Condition code
Surgery 297702 297702 0 0
Other surgery
Anaesthesiology 297703 297703 0 0
Anaesthetics
Cancer 297704 297704 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Goal-directed Therapy/Experimental Group

Patients undergoing Liver Resection in the Goal Directed Therapy (GDT) group (experimental group) will have a Flotrac/Vigileo device TradeMark connected after insertion of the arterial line. The arterial catheters will be connected to the cardiac output device transducer system and haemodynamic data from the Flotrac device will be collected throughout surgery. All transducers will be zeroed to atmospheric pressure at the level of the right atrium.

Patients in the GDT group will be managed by a Stroke Ventricular Volume (SVV) guided protocol to maintain SVV < 20%. This percentage of SVV is frequently used in our institution as a target for patients undergoing this procedure. For the GDT group, if SVV remains above 20% for at least 2 min, then a 250mL bolus of balanced crystalloid (Hartmanns solution or Plasmalyte) or colloid fluid (Albumen) will be given. The SVV will be assessed every 20 seconds via the FloTrac/Vigileo proprietary algorithm. Similar to other GDT studies, the preferred colloid will be albumin secondary to the known effects of improved intravascular repletion and intravascular half life and the theoretical benefit of prolonged stroke volume optimization. In both groups, the administration of blood products will be at the discretion of the anaesthetist, as clinically indicated. There will be no standard protocol for fluid maintenance infusion for either group.

The GDT group will receive standard perioperative Enhanced Recovery After Surgery (ERAS) care and additional haemodynamic monitoring using the FloTrac/Vigileo TradeMark (Edwards Lifesciences, Irvine, CA).

The anaesthetist will have no influence over any aspect of postoperative care management. All clinicians and nursing staff in charge of postoperative care will be blinded to the allocation of patients. The Flotrac system will be connected to the patient prior to surgical incision and discontinued as soon as the surgery is complete.
Intervention code [1] 293855 0
Treatment: Devices
Comparator / control treatment
Control group

Patients undergoing Major Liver Resection in the control group will have a Flotrac/Vigileo deviceTM connected after insertion of the arterial line. The arterial catheters will be connected to the cardiac output device transducer system and haemodynamic data from the Flotrac device will be collected throughout surgery. All transducers will be zeroed to atmospheric pressure at the level of the right atrium.

Control patients will have fluid management and inotropic use guided by the routine cardiovascular monitoring in place i.e. arterial line, and central venous catheter, which will be at the discretion of the anaesthetist, who will be blinded to Flotrac data. The Control group anaesthetist will be allowed to have the Flotrac haemodynamic data unblinded if needed for
clinical decision making but patients will be removed from analysis if this occurs.

In both groups, the administration of blood products will be at the discretion of the anaesthetist, as clinically indicated. There will be no standard protocol for fluid maintenance infusion for either group.

The control group will receive standard perioperative Enhanced Recovery After Surgery (ERAS) care alone.

The anaesthetist will have no influence over any aspect of postoperative care management. All clinicians and nursing staff in charge of postoperative care will be blinded to the allocation of patients. The Flotrac system will be connected to the patient prior to surgical incision and discontinued as soon as the surgery is complete.
Control group
Active

Outcomes
Primary outcome [1] 297284 0
Duration of hospital stay in hours. Data for length of stay will collected from our hospitals electronic medical records.
Timepoint [1] 297284 0
This will be calculated as number of hours beginning from surgical closure to hospital discharge.
Secondary outcome [1] 320599 0
Cardiac Output

This variable will be measured via pulse contour analyses from the Flotrac sensor
Timepoint [1] 320599 0
Intraoperative: Prior to surgical incision and at completion of surgery
Secondary outcome [2] 320600 0
Cardiac Index

This variable will be measured via pulse contour analyses from the Flotrac sensor
Timepoint [2] 320600 0
Intraoperative: Prior to surgical incision and at completion of surgery
Secondary outcome [3] 320601 0
Mean Arterial Pressure

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [3] 320601 0
Intraoperative: Prior to surgical incision and at completion of surgery
Secondary outcome [4] 320602 0
Stroke Volume Variation

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [4] 320602 0
Intraoperative: Prior to surgical incision and at completion of surgery
Secondary outcome [5] 320603 0
Systemic Vascular Resistance

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [5] 320603 0
Intraoperative: Prior to surgical incision and at completion of surgery
Secondary outcome [6] 320604 0
Heart Rate

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [6] 320604 0
Intraoperative: Prior to surgical incision and at completion of surgery
Secondary outcome [7] 320605 0
Percentage of participants who develop pulmonary congestion defined as accumulation of fluid in the air spaces and parenchyma of the lungs resulting in impaired gas exchange during hospital stay post surgery.
Timepoint [7] 320605 0
Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital
Secondary outcome [8] 320606 0
Percentage of participants who develop Pneumonia defined as elevated temperature and elevated white cell count with radiological confirmation during hospital stay post surgery. .
Timepoint [8] 320606 0
Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital
Secondary outcome [9] 320607 0
Percentage of participants who develop Heart Failure defined as the heart being unable to maintain adequate circulation of blood in the tissues of the body or to pump out the venous blood returned to it by the venous circulation during hospital stay post surgery. This will be measured with elevated Brain natriuretic peptile and echocardiography.
Timepoint [9] 320607 0
Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital.
Secondary outcome [10] 320608 0
Percentage of participants who develop cardiac arrythmias defined as ECG changes requiring medical treatment or cardioversion or heart rate <50beats/min requiring medical treatment/pacing during hospital stay post surgery.
Timepoint [10] 320608 0
Duration of hospital stay. Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital.
Secondary outcome [11] 320609 0
Percentage of participants who develop Acute Kidney Injury defined the RIFLE Citeria during hospital stay post surgery. Data from in patient medical records which will include serum creatinine, estimated glomerular filtration rate and urine output, will be used to assess this.
Timepoint [11] 320609 0
Duration of hospital stay.
Secondary outcome [12] 320610 0
Percentage of participants who develop Intra-abdominal collection defined as a collection of pus or fluid inside the abdomen during hospital stay post surgery. This will be defined by abdominal ultrasound or computed tomography.
Timepoint [12] 320610 0
Duration of hospital stay. Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital
Secondary outcome [13] 320611 0
Percentage of participants who develop Post operative bleeding defined by change in haemoglobin concentrations and/or blood from surgical drains during hospital stay post surgery.
Timepoint [13] 320611 0
Duration of hospital stay. Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital
Secondary outcome [14] 320613 0
Percentage of participants who develop Delayed Gastric Emptying defined as a slowed or complete cessation of movement of food from the stomach to the small intestine during hospital stay post surgery.
Timepoint [14] 320613 0
Duration of hospital stay. Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital.
Secondary outcome [15] 320614 0
Percentage of participants requiring blood transfusions during hospital stay post surgery.
Timepoint [15] 320614 0
Duration of hospital stay. Data will be collected from medical charts and occurrence of the above outcome noted once patient is discharged from the hospital
Secondary outcome [16] 320617 0
Percentage of participants who require Use of inotropes (type, amount, duration) during surgery.
Timepoint [16] 320617 0
Data will be collected from the patients anaesthesia records.
Secondary outcome [17] 320618 0
Duration of ICU stay in hours form admission to ICU un til discharge from ICU. Data from in patient medical records will be used to assess this.
Timepoint [17] 320618 0
Postoperative period for the duration of the ICU stay.

Eligibility
Key inclusion criteria
All patients (age > 18 years) undergoing liver resection
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age less than 18 years
2. Abnormal pre-operative coagulopathy: INR (international normalised ratio) > 1.5, platelet count < 75 x 109/l
3. Severe hepatic insufficiency (bilirubin > 30umol/L, ALP (alkaline phosphatase) >300iu/L, ALT (alanine transaminase) > 50iu/L, albumin < 25g/dL, INR > 1.5)
4. Severe renal impairment: Serum Creatinine >250ummol/L
5. American Society of Anaesthesiologists (ASA) physical status IV or V

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All adult patients undergoing liver resection will be evaluated preoperatively at the anaesthesia pre-admsissions clinic at least 1-2 weeks prior to surgery. Patients will be identified for study entry by the investigators or an anaesthetist or research co-ordinator acting on behalf of the principal investigators by surveillance of patients in the pre-admissions clinic.

Patients will be identified from their preoperative medical records and surgical notes.

A thorough assessment of the participant’s competence and capacity to make a valid informed decision will be made by the study investigators prior to the patient being recruited. All patients will be deemed competent if they:
1. Able to comprehend and retain information relevant to making the decision
2. Understand the information and implications of the decision
3. Able to weigh the information in the balance and arrive at a decision

For each patient, an opaque envelope containing a participant number will be prepared, sealed and sequentially numbered. On the morning of surgery the anaesthetist will open the envelope and randomise the participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation using computer generated software will be used
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will recruit 50 patients in total, 25 patients in the GDT group and 25 patients in the
standard group. This is in keeping with realistic power calculations used in other studies evaluating the use of GDT in patients undergoing major abdominal surgery. Canesson’s group in the US detect a 3-day mean length of stay difference between the two groups, with a standard deviation of 3 days in each group, a two tailed alpha of 0.05 and power of 0.80, and calculated that a minimum of 17 subjects were required in each group. They assumed that a similar sample size would be needed to detect a similar difference in time to return of GI function. Also, since they expected similar results between arterial pressure waveform analysis technology used for their study and the oesophageal Doppler technology used for other referenced studies, it was felt that this estimation was appropriate.

Sample size for the study was calculated based on our pilot data evaluating patients
undergoing liver resection with an ERAS program at Austin hospital. With an median length of hospital stay of 6 days, and a SD of 1.5 days, if we were to demonstrate a mean
difference between the control group and the GDT group of 1 day, with a power value of
90%, we require a minimum of 24 patients to be recruited into each group.

We will therefore recruit 25 patients in each arm, a total of 50 patients.

Statistical analysis will be performed using computerized software (SPSS for windows 12.0). For data that was non-normally distributed a Mann-Whitney U-test will be used and normally distributed data will be compared using Student’s t-test. Ordinal and nominal data will be compared using Chi-squared analysis. A p value < 0.05 will be considered significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
9/09/2013
Date of last participant enrolment
Anticipated
31/03/2016
Actual
23/05/2016
Date of last data collection
Anticipated
Actual
1/06/2016
Sample size
Target
48
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5239 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 5240 0
Warringal Private Hospital - Heidelberg
Recruitment hospital [3] 5242 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [4] 5243 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 5244 0
Box Hill Hospital - Box Hill
Recruitment postcode(s) [1] 12709 0
3084 - Heidelberg
Recruitment postcode(s) [2] 12710 0
3002 - East Melbourne
Recruitment postcode(s) [3] 12711 0
3168 - Clayton
Recruitment postcode(s) [4] 12712 0
3152 - Wantirna

Funding & Sponsors
Funding source category [1] 292847 0
Hospital
Name [1] 292847 0
Austin Hospital
Country [1] 292847 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Department of Anaesthesia
Studley Road
Heidelberg, Victoria, 3084
Country
Australia
Secondary sponsor category [1] 291592 0
None
Name [1] 291592 0
N/A
Address [1] 291592 0
N/A
Country [1] 291592 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294348 0
Austin Hospital Research Ethics Committee
Ethics committee address [1] 294348 0
Ethics committee country [1] 294348 0
Australia
Date submitted for ethics approval [1] 294348 0
23/04/2013
Approval date [1] 294348 0
03/09/2013
Ethics approval number [1] 294348 0
HREC/13/Austin/31

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63274 0
A/Prof Laurence Weinberg
Address 63274 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 63274 0
Australia
Phone 63274 0
+61 3 94965000
Fax 63274 0
+61 3 94596421
Email 63274 0
[email protected]
Contact person for public queries
Name 63275 0
Laurence Weinberg
Address 63275 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 63275 0
Australia
Phone 63275 0
+61 3 94965000
Fax 63275 0
+61 3 94596421
Email 63275 0
[email protected]
Contact person for scientific queries
Name 63276 0
Laurence Weinberg
Address 63276 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 63276 0
Australia
Phone 63276 0
+61 3 94965000
Fax 63276 0
+61 3 94596421
Email 63276 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseGoal directed fluid therapy for major liver resection: A multicentre randomized controlled trial.2019https://dx.doi.org/10.1016/j.amsu.2019.07.003
N.B. These documents automatically identified may not have been verified by the study sponsor.