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Trial registered on ANZCTR


Registration number
ACTRN12616000538448
Ethics application status
Approved
Date submitted
8/02/2016
Date registered
27/04/2016
Date last updated
7/07/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Goal-directed Therapy for Patients Undergoing Pancreaticoduodenectomy
Scientific title
A Prospective Multicentre Randomized Controlled Trial of Standard Compared to Surgery Specific Goal-directed Therapy (GDT) for Patients Undergoing
Pancreaticoduodenectomy
Secondary ID [1] 288470 0
Nil
Universal Trial Number (UTN)
U1111-1179-1357
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic cancer 297506 0
Condition category
Condition code
Surgery 297699 297699 0 0
Other surgery
Anaesthesiology 297700 297700 0 0
Anaesthetics
Cancer 297701 297701 0 0
Pancreatic

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

Patients undergoing pancreaticoduodenectomy 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] 293854 0
Treatment: Devices
Comparator / control treatment
Control group

Patients undergoing pancreaticoduodenectomy in the control 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.

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] 297282 0
Duration of hospital stay in hours. This will be calculated as number of hours beginning from completion of surgery to hospital discharge. Data from our institutions patient medical records will be used to assess this.
Timepoint [1] 297282 0
Postoperative period, which will be from completion fo surgery to discharge form hospital.
Secondary outcome [1] 320579 0
Cardiac Output

This variable will be measured via pulse contour analyses using Flotrac sensor
Timepoint [1] 320579 0
Intraoperatively: immediately prior to surgical incision until completion of surgery
Secondary outcome [2] 320580 0
Cardiac Index

This variable will be measured via pulse contour analyses using Flotrac sensor
Timepoint [2] 320580 0
Intraoperatively: prior to surgical incision until completion of surgery
Secondary outcome [3] 320581 0
Mean Arterial Pressure

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [3] 320581 0
Intraoperatively: immediately prior to surgical incision until completion of surgery
Secondary outcome [4] 320582 0
Stroke Volume Variation

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [4] 320582 0
Intraoperatively: immediately prior to surgical incision until completion of surgery
Secondary outcome [5] 320583 0
Systemic Vascular Resistance

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [5] 320583 0
Intraoperatively: immediately prior to surgical incision until completion of surgery
Secondary outcome [6] 320584 0
Heart Rate

This variable will be measured via pressure readings from the Flotrac sensor
Timepoint [6] 320584 0
Intraoperatively: immediately prior to surgical incision until completion of surgery
Secondary outcome [7] 320585 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. Data from in patient medical records will be used to assess this.
Timepoint [7] 320585 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 [8] 320586 0
Percentage of participants who develop Pneumonia defined as elevated temperature and elevated white cell count with radiological confirmation during hospital stay post surgery. Data from in patient medical records will be used to assess this.
Timepoint [8] 320586 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 [9] 320587 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. Data from in patient medical records will be used to assess this.
Timepoint [9] 320587 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 [10] 320588 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. Data from in patient medical records will be used to assess this.
Timepoint [10] 320588 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] 320589 0
Percentage of participants who develop Acute Kidney Injury defined the RIFLE Citeria during hospital stay post surgery. Data from in patient medical records will be used to assess this.
Timepoint [11] 320589 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 [12] 320590 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. Data from in patient medical records will be used to assess this.
Timepoint [12] 320590 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] 320591 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. Data from in patient medical records will be used to assess this.
Timepoint [13] 320591 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] 320592 0
Percentage of participants who develop Pancreatic anastomotic leakage defined as failure of healing/sealing of a pancreatic-enteric anastomosis during hospital stay post surgery. Data from in patient medical records will be used to assess this.
Timepoint [14] 320592 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] 320593 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. Data from in patient medical records will be used to assess this.
Timepoint [15] 320593 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] 320594 0
Percentage of participants requiring blood transfusions during hospital stay post surgery. Data from in patient medical records will be used to assess this.
Timepoint [16] 320594 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 [17] 320597 0
Percentage of participants who require Use of inotropes (type, amount, duration) during surgery. Data from in patient medical records will be used to assess this.
Timepoint [17] 320597 0
Intraoperatively: immediately prior to surgical incision until completion of surgery
Secondary outcome [18] 320598 0
Duration of ICU stay in hours. Data from in patient medical records will be used to assess this.
Timepoint [18] 320598 0
Postoperative period

Eligibility
Key inclusion criteria
All patients (age > 18 years) undergoing pancreaticoduodenectomy
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 pancreaticoduodenectomy 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 were deemed competent if they:
1. are 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 was prepared, sealed and sequentially numbered. On the morning of surgery the anaesthetist opened the envelope and randomised the participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation using computer generated software was 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 powered this Trial to observe a large treatment effect (Cohen’s d = 0.8). In order to observe such effect 52 patients in total (26 per group) would provide a power of 0.8, assuming the type 1 error threshold of 0.05. This is a larger sample size compared to realistic power calculations used in other studies evaluating the use of GDT in patients undergoing major abdominal surgery. Canesson’s group in the US detected 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. Based on pilot data from our institution, the expected LOS in the control group was 16 days (SD=4 days). Effects size d =0.8 would correspond to the difference of 3.2 days (similar to Canesson et al), thus the expected LOS in intervention group would be 12.8 days.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
9/09/2013
Date of last participant enrolment
Anticipated
28/03/2016
Actual
31/12/2015
Date of last data collection
Anticipated
Actual
31/01/2016
Sample size
Target
52
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5236 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 5237 0
Warringal Private Hospital - Heidelberg
Recruitment hospital [3] 5238 0
Knox Private Hospital - Wantirna
Recruitment postcode(s) [1] 12707 0
3084 - Heidelberg
Recruitment postcode(s) [2] 12708 0
3152 - Wantirna

Funding & Sponsors
Funding source category [1] 292846 0
Hospital
Name [1] 292846 0
Austin Hospital
Country [1] 292846 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Department of Anaesthesia
Studley Road
Heidelberg, Victoria, 3084
Country
Australia
Secondary sponsor category [1] 291591 0
None
Name [1] 291591 0
N/A
Address [1] 291591 0
N/A
Country [1] 291591 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294347 0
Austin Hospital Research Ethics Committee
Ethics committee address [1] 294347 0
Studley Road, Heidelberg, Victoria, 3084, Australia
Ethics committee country [1] 294347 0
Australia
Date submitted for ethics approval [1] 294347 0
23/04/2013
Approval date [1] 294347 0
02/09/2013
Ethics approval number [1] 294347 0
HREC/13/Austin/30

Summary
Brief summary
This study aims to evaluate if patients undergoing pancreaticoduodenectomy (Whipple’s procedure) managed by intraoperative goal directed therapy with the Flotrac/Vigileo deviceTM will have a shorter length of hospital stay with fewer post-operative complications compared to patients managed by standard care.

Who is it for? You may be eligible to join this study if you are aged 18 years or more and are scheduled to undergo pancreaticoduodenectomy (Whipple procedure).

Study details: Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will have their haemodynamic variables (fluid dynamic and blood flow) managed by intraoperative goal directed therapy (GDT) using the Flotrac/Vigileo deviceTM (FloTrac/Vigileo Version 3.02, Edwards Lifesciences, Irvine, CA, USA). This minimally invasive device automatically calculates key flow parameters every 20 seconds and recognizes and allows for adjustments in haemodynamic variables in patients undergoing major surgery. Importantly, it enables the anaesthetist to make a differential diagnosis leading to either a volume or cardiovascular intervention (preload, afterload and contractility), by providing continuous information on the patients cardiac output, stroke volume, and systemic vascular resistance. Participants allocated to the control group 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. There is now compelling evidence that fluid optimization and GDT in patients undergoing colorectal surgery leads to better outcomes, particularly in high risk patients.

This study will contribute to understanding if similar benefit of GDT is also observed in patients undergoing major pancreatic surgery - pancreaticoduodenectomy (Whipples Procedure).
Trial website
N/A
Trial related presentations / publications
Nil publications to date
Public notes

Contacts
Principal investigator
Name 63270 0
A/Prof Laurence Weinberg
Address 63270 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 63270 0
Australia
Phone 63270 0
+61 3 94965000
Fax 63270 0
+61 3 94596421
Email 63270 0
[email protected]
Contact person for public queries
Name 63271 0
Laurence Weinberg
Address 63271 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 63271 0
Australia
Phone 63271 0
+61 3 94965000
Fax 63271 0
+61 3 94596421
Email 63271 0
[email protected]
Contact person for scientific queries
Name 63272 0
Laurence Weinberg
Address 63272 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 63272 0
Australia
Phone 63272 0
+61 3 94965000
Fax 63272 0
+61 3 94596421
Email 63272 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
EmbaseRestrictive intraoperative fluid optimisation algorithm improves outcomes in patients undergoing pancreaticoduodenectomy: A prospective multicentre randomized controlled trial.2017https://dx.doi.org/10.1371/journal.pone.0183313
N.B. These documents automatically identified may not have been verified by the study sponsor.