Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Glycocalyx Levels in Patients Undergoing Pancreatectomy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04058236
Recruitment Status : Not yet recruiting
First Posted : August 15, 2019
Last Update Posted : August 16, 2019
Sponsor:
Information provided by (Responsible Party):
Dr Loh Pui San, University of Malaya

Tracking Information
First Submitted Date  ICMJE August 9, 2019
First Posted Date  ICMJE August 15, 2019
Last Update Posted Date August 16, 2019
Estimated Study Start Date  ICMJE August 15, 2019
Estimated Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
  • Occurence of pancreatic fistula leak [ Time Frame: Within post-op 30 days ]
    Review will be done according to guideline of Revised 2016 International Study Group on Pancreatic Fistula (ISGPF)
  • Changes in serum syndecan 1 concentrations [ Time Frame: Within post-op 7 days ]
    Blood samples are collected to check for syndecan 1 concentrations in serum
  • Changes in serum heparan sulfate concentrations [ Time Frame: Within post-op 7 days ]
    Blood samples are collected to check for heparan sulfate concentrations in serum
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04058236 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
Changes in levels of Inflammatory markers Interleukin-1 and CRP [ Time Frame: Within post-op 7 days ]
Blood samples are collected to check level of the Inflammatory markers Interleukin-1 and CRP
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Glycocalyx Levels in Patients Undergoing Pancreatectomy
Official Title  ICMJE Glycocalyx Levels in Patients Undergoing Pancreatectomy With Human Albumin 5% vs. Gelofusine
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.

Detailed Description

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized control trial with Albumin 5% given as the intervention and Gelofusine as active control.
Masking: Double (Participant, Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Treatment
Condition  ICMJE
  • Endothelial Degeneration
  • Pancreatic Cancer
  • Pancreatectomy
  • Postoperative Pancreatic Fistula
Intervention  ICMJE
  • Other: 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.
    Other Name: Fluid management
  • 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.
    Other Name: Fluid management
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Other: human albumin 5%
  • Active Comparator: gelofusine
    10 patients with pancreatic cancer will receive gelofusine in a restrictive goal directed fluid regime preoperatively for the first 24 hours.
    Intervention: Other: gelofusine.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 13, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2021
Estimated Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pui San Loh, MBBS, MMed 012-2268285 lohps@ummc.edu.my
Contact: Sook Hui Chaw, MD sook_hui@ummc.edu.my
Listed Location Countries  ICMJE Malaysia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04058236
Other Study ID Numbers  ICMJE U1111-1237-9121
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dr Loh Pui San, University of Malaya
Study Sponsor  ICMJE University of Malaya
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pui San Loh, MBBS, MMed University Malaya, Malaysia
PRS Account University of Malaya
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP