Glycocalyx Levels in Patients Undergoing Pancreatectomy

NCT04058236 | Unknown Phase 4

• 1 other identifier: U1111-1237-9121
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Endothelial Degeneration; Pancreatic Cancer; Pancreatectomy; Postoperative Pancreatic Fistula

Keywords

Glycocalyx levels; pancreatectomy; human albumin 5%; gelofusine; pancreatic fistula

Outcome Measures

Primary Outcomes (3)

• Occurence of pancreatic fistula leak

  Review will be done according to guideline of Revised 2016 International Study Group on Pancreatic Fistula (ISGPF)

  Within post-op 30 days

• Changes in serum syndecan 1 concentrations

  Blood samples are collected to check for syndecan 1 concentrations in serum

  Within post-op 7 days

• Changes in serum heparan sulfate concentrations

  Blood samples are collected to check for heparan sulfate concentrations in serum

  Within post-op 7 days

Secondary Outcomes (1)

• Changes in levels of Inflammatory markers Interleukin-1 and CRP

  Within post-op 7 days

Study Arms (2)

human albumin 5%

EXPERIMENTAL

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

Other: human albumin 5%

gelofusine

ACTIVE COMPARATOR

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

Other: gelofusine.

Interventions

human albumin 5% 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.

Also known as: Fluid management

human albumin 5%

gelofusine. 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.

Also known as: Fluid management

gelofusine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Malaya: lead

Study Sites (1)

Anaesthesia Department, Faculty of Medicine, University Malaya

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

RECRUITING

Related Publications (15)

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

  PMID: 16999215 BACKGROUND

• 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.

  PMID: 22290457 BACKGROUND

• 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.

  PMID: 22009311 BACKGROUND

• 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.

  PMID: 26749537 BACKGROUND

• Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet. 2002 May 25;359(9320):1812-8. doi: 10.1016/S0140-6736(02)08711-1.

  PMID: 12044376 BACKGROUND

• 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.

  PMID: 25497357 BACKGROUND

• 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.

  PMID: 30370053 BACKGROUND

• 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.

  PMID: 17196565 BACKGROUND

• 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.

  PMID: 24773303 BACKGROUND

• Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Moller MH, Elkjaer JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Soe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjaeldgaard AL, Fabritius ML, Mondrup F, Pott FC, Moller TP, Winkel P, Wetterslev J; 6S Trial Group; Scandinavian Critical Care Trials Group. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med. 2012 Jul 12;367(2):124-34. doi: 10.1056/NEJMoa1204242. Epub 2012 Jun 27.

  PMID: 22738085 BACKGROUND

• 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.

  PMID: 23075127 BACKGROUND

• Vincent JL, Russell JA, Jacob M, Martin G, Guidet B, Wernerman J, Ferrer R, McCluskey SA, Gattinoni L. Albumin administration in the acutely ill: what is new and where next? Crit Care. 2014 Jul 16;18(4):231. doi: 10.1186/cc13991.

  PMID: 25042164 BACKGROUND

• Cooper DJ, Myburgh J, Heritier S, Finfer S, Bellomo R, Billot L, Murray L, Vallance S; SAFE-TBI Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Albumin resuscitation for traumatic brain injury: is intracranial hypertension the cause of increased mortality? J Neurotrauma. 2013 Apr 1;30(7):512-8. doi: 10.1089/neu.2012.2573. Epub 2013 Mar 21.

  PMID: 23194432 BACKGROUND

• Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004 May 27;350(22):2247-56. doi: 10.1056/NEJMoa040232.

  PMID: 15163774 BACKGROUND

• Kang H, Wu Q, Sun A, Liu X, Fan Y, Deng X. Cancer Cell Glycocalyx and Its Significance in Cancer Progression. Int J Mol Sci. 2018 Aug 22;19(9):2484. doi: 10.3390/ijms19092484.

  PMID: 30135409 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms; Pancreatic Fistula

Interventions

Polygeline

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Digestive System Fistula; Fistula; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polymers; Macromolecular Substances; Peptides; Amino Acids, Peptides, and Proteins; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Pui San Loh, MBBS, MMed

  University Malaya, Malaysia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pui San Loh, MBBS, MMed

CONTACT

012-2268285; lohps@ummc.edu.my

Sook Hui Chaw, MD

CONTACT

sook_hui@ummc.edu.my

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Anaesthesiologist

Model Details: Randomized control trial with Albumin 5% given as the intervention and Gelofusine as active control.

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 15, 2019
• Study Start: August 15, 2019
• Primary Completion: July 15, 2021
• Study Completion: July 31, 2021
• Last Updated: April 30, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)