ANZCTR - Registration

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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]

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

Condition category

Condition code

Surgery

Other surgery

Anaesthesiology

Anaesthetics

Cancer

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]

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]

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]

Postoperative period, which will be from completion fo surgery to discharge form hospital.

Secondary outcome [1]

Cardiac Output

This variable will be measured via pulse contour analyses using Flotrac sensor

Timepoint [1]

Intraoperatively: immediately prior to surgical incision until completion of surgery

Secondary outcome [2]

Cardiac Index

This variable will be measured via pulse contour analyses using Flotrac sensor

Timepoint [2]

Intraoperatively: prior to surgical incision until completion of surgery

Secondary outcome [3]

Mean Arterial Pressure

This variable will be measured via pressure readings from the Flotrac sensor

Timepoint [3]

Intraoperatively: immediately prior to surgical incision until completion of surgery

Secondary outcome [4]

Stroke Volume Variation

This variable will be measured via pressure readings from the Flotrac sensor

Timepoint [4]

Intraoperatively: immediately prior to surgical incision until completion of surgery

Secondary outcome [5]

Systemic Vascular Resistance

This variable will be measured via pressure readings from the Flotrac sensor

Timepoint [5]

Intraoperatively: immediately prior to surgical incision until completion of surgery

Secondary outcome [6]

Heart Rate

This variable will be measured via pressure readings from the Flotrac sensor

Timepoint [6]

Intraoperatively: immediately prior to surgical incision until completion of surgery

Secondary outcome [7]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Intraoperatively: immediately prior to surgical incision until completion of surgery

Secondary outcome [18]

Duration of ICU stay in hours. Data from in patient medical records will be used to assess this.

Timepoint [18]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

Warringal Private Hospital - Heidelberg

Recruitment hospital [3]

Knox Private Hospital - Wantirna

Recruitment postcode(s) [1]

3084 - Heidelberg

Recruitment postcode(s) [2]

3152 - Wantirna

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Austin Hospital

Address [1]

Department of Anaesthesia
Studley Road
Heidelberg, Victoria, 3084

Country [1]

Australia

Primary sponsor type

Hospital

Name

Austin Hospital

Address

Department of Anaesthesia
Studley Road
Heidelberg, Victoria, 3084

Country

Australia

Secondary sponsor category [1]

None

Name [1]

N/A

Address [1]

N/A

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Hospital Research Ethics Committee

Ethics committee address [1]

Studley Road, Heidelberg, Victoria, 3084, Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/04/2013

Approval date [1]

02/09/2013

Ethics approval number [1]

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

A/Prof Laurence Weinberg

Address

Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Fax

+61 3 94596421

[email protected]

Contact person for public queries

Name

A/Prof Laurence Weinberg

Address

Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Fax

+61 3 94596421

[email protected]

Contact person for scientific queries

Name

A/Prof Laurence Weinberg

Address

Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Fax

+61 3 94596421

[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

Source	Title	Year of Publication	DOI
Embase	Restrictive intraoperative fluid optimisation algorithm improves outcomes in patients undergoing pancreaticoduodenectomy: A prospective multicentre randomized controlled trial.	2017	https://dx.doi.org/10.1371/journal.pone.0183313

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically