Glycocalyx Levels in Patients Undergoing Pancreatectomy

NCT ID: NCT04058236

Last Updated: 2020-04-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-15

Study Completion Date

2021-07-31

Brief Summary

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Background:

On the surface of every healthy cellular membrane resides a layer known as the glycocalyx. This structure consists of extracellular domains of receptor, adhesion and transmembrane molecules such as syndecan-1 covalently bound to highly negatively charged glycosaminoglycans, heparan sulfates. It has a principal role to maintain wall integrity, avoid inflammation and tissue oedema in vessels but in contrast, glycocalyx is robust and elevated on cancer cells. This study examines whether the endothelial glycocalyx layer is preserved in patients undergoing pancreatectomy with human albumin 5% vs. gelofusine in a restrictive goal directed fluid regime perioperatively for the first 24hours. Degradation of glycocalyx will be investigated by analyzing basic levels of the core protein syndecan-1 and heparan sulfates with post-operative samples.

Detailed Description

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This is a prospective study that will be conducted in the Main Operating theatres of UMMC on patients with pancreatic cancer undergoing elective pancreatectomy (includes all forms of pancreatectomy such as Whipple's procedure, total or distal pancreatectomy).

This study aim to determine the association of glycocalyx degradation by measuring levels of syndecan-1 and heparan sulfate with type of colloidal fluid given, human albumin 5% versus gelofusine in a restrictive goal directed fluid therapy in pancreatectomy.

Institutional ethics approval and registration in Clinical Trial Registry will be obtained before recruiting the first case.

Recruited patients will be randomly allocated to either the group receiving human albumin 5% or gelofusine.

Sample size:

There is no previously published literature related exactly to the pathology and methods of this proposed study. Therefore, a preliminary sample size calculation will be based on the closest study on fluids with a two-sided confidence interval of 0.95 and a desired power of 0.80 to yield a result that investigators need nine patients in each group. After adjusting for drop out rate of 10%, investigators will recruit ten in each group for human albumin 5% and gelofusine respectively within the study period of 2 years.

Data collection:

1. Intraoperative phase All preoperative preparation including fasting will be done in accordance to UMMC protocol. Intraoperative monitoring includes standard routine monitoring as per American Society of Anaesthesiologist Guidelines, invasive haemodynamic monitoring with arterial blood pressure incorporating FloTrac, BIS and neuromuscular monitoring. All patients will be under general anesthesia.

Fluid management for both groups are in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. If SVV is \> 15%, 250ml of fluid replacement according to patient group will be given over 30 min within 24 hours intra and post operatively in the Intensive Care Unit (ICU). In both groups, all clinical parameters and fluids including blood that will be given will be recorded.
2. Post-operative phase:

The allocated colloid fluid will be continued.

Patients will be assessed for pancreatic fistula leak. The grading of pancreatic fistula will be defined according to the guideline of Revised 2016 International Study Group on Pancreatic Fistula (ISGPF).

Reviews will be done on post op days 1, 3, 5 and 30. Amylase levels from drain tube post-op Day 3, 5 and 7 will be measured. The total duration of stay in intensive care, hospital and rate of mortality/ morbidity (re-laparotomy/ re-admission to ICU/ sepsis) within 30 days after surgery will be assessed and recorded.
3. Laboratory phase Blood samples are collected at 5 time points, a) preoperative, b) immediate postoperative and c) 24 hours postoperative d) Day 3 and e) Day 7 postoperative from both groups. The serum fraction will be frozen and stored at -80°C until assayed. Syndecan 1 concentrations and heparan sulfate concentrations are quantified using special enzyme-linked immunosorbent assay kit as previously reported. Inflammatory markers Interleukin-1 and CRP and any blood investigations as per hospital sepsis protocol will be determined as well.

Conditions

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Endothelial Degeneration Pancreatic Cancer Pancreatectomy Postoperative Pancreatic Fistula

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized control trial with Albumin 5% given as the intervention and Gelofusine as active control.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Randomized concealed assignment into 2 groups in opaque envelopes will be opened by care provider. Anaesthetic and ICU notes must not be revealed to outcome assessor.

Study Groups

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human albumin 5%

10 patients with pancreatic cancer will receive human albumin 5% in a restrictive goal directed fluid regime preoperatively for the first 24 hours.

Group Type EXPERIMENTAL

human albumin 5%

Intervention Type OTHER

Human Albumin 5% will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.

gelofusine

10 patients with pancreatic cancer will receive gelofusine in a restrictive goal directed fluid regime preoperatively for the first 24 hours.

Group Type ACTIVE_COMPARATOR

gelofusine.

Intervention Type OTHER

Gelofusine will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.

Interventions

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human albumin 5%

Human Albumin 5% will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.

Intervention Type OTHER

gelofusine.

Gelofusine will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.

Intervention Type OTHER

Other Intervention Names

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Fluid management Fluid management

Eligibility Criteria

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Inclusion Criteria

* ASA 1-3
* patients aged between 18-75 years old with written informed consent

Exclusion Criteria

* Patients who refuse to participate,
* Have severe congestive heart failure (NYHA class III/IV) or severe respiratory disease (PaO2/FiO2 \< 200),
* Suffer significant renal or hepatic dysfunction (creatinine raised \>50 % or liver enzymes \>50 % of normal values),
* Pregnant
* Allergic to gelofusine and human albumin
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Malaya

OTHER

Sponsor Role lead

Responsible Party

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Dr Loh Pui San

Consultant Anaesthesiologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pui San Loh, MBBS, MMed

Role: PRINCIPAL_INVESTIGATOR

University Malaya, Malaysia

Locations

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Anaesthesia Department, Faculty of Medicine, University Malaya

Kuala Lumpur, Kuala Lumpur, Malaysia

Site Status RECRUITING

Countries

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Malaysia

Central Contacts

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Pui San Loh, MBBS, MMed

Role: CONTACT

012-2268285

Sook Hui Chaw, MD

Role: CONTACT

Facility Contacts

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Pui San Loh, FANZCA

Role: primary

+60379492052

References

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Pries AR, Kuebler WM. Normal endothelium. Handb Exp Pharmacol. 2006;(176 Pt 1):1-40. doi: 10.1007/3-540-32967-6_1.

Reference Type BACKGROUND
PMID: 16999215 (View on PubMed)

Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth. 2012 Mar;108(3):384-94. doi: 10.1093/bja/aer515. Epub 2012 Jan 29.

Reference Type BACKGROUND
PMID: 22290457 (View on PubMed)

Curry FE, Adamson RH. Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng. 2012 Apr;40(4):828-39. doi: 10.1007/s10439-011-0429-8. Epub 2011 Oct 19.

Reference Type BACKGROUND
PMID: 22009311 (View on PubMed)

Tarbell JM, Cancel LM. The glycocalyx and its significance in human medicine. J Intern Med. 2016 Jul;280(1):97-113. doi: 10.1111/joim.12465. Epub 2016 Jan 8.

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Reference Type BACKGROUND
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Chappell D, Bruegger D, Potzel J, Jacob M, Brettner F, Vogeser M, Conzen P, Becker BF, Rehm M. Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx. Crit Care. 2014 Oct 13;18(5):538. doi: 10.1186/s13054-014-0538-5.

Reference Type BACKGROUND
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Sulzer JK, Sastry AV, Meyer LM, Cochran A, Buhrman WC, Baker EH, Martinie JB, Iannitti DA, Vrochides D. The impact of intraoperative goal-directed fluid therapy on complications after pancreaticoduodenectomy. Ann Med Surg (Lond). 2018 Oct 16;36:23-28. doi: 10.1016/j.amsu.2018.10.018. eCollection 2018 Dec.

Reference Type BACKGROUND
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Jacob M, Bruegger D, Rehm M, Stoeckelhuber M, Welsch U, Conzen P, Becker BF. The endothelial glycocalyx affords compatibility of Starling's principle and high cardiac interstitial albumin levels. Cardiovasc Res. 2007 Feb 1;73(3):575-86. doi: 10.1016/j.cardiores.2006.11.021. Epub 2006 Nov 21.

Reference Type BACKGROUND
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Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia. 2014 Jul;69(7):777-84. doi: 10.1111/anae.12661. Epub 2014 Apr 28.

Reference Type BACKGROUND
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Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Rajbhandari D, Taylor CB, Webb SA; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012 Nov 15;367(20):1901-11. doi: 10.1056/NEJMoa1209759. Epub 2012 Oct 17.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Other Identifiers

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U1111-1237-9121

Identifier Type: -

Identifier Source: org_study_id

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