Evaluation of Endothelial Glycocalyx in the Surgical Resuscitation of Major Burn Patients

NCT06670248 | Recruiting

• 1 other identifier: PR(AT)400/2023
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this observational study is to examine whether Endotheliopathy of Trauma (EoT) is present in severely burned patients and how it is affected by burn debridement surgery. The main questions it aims to answer are:

• Do severely burned patients present with EoT before undergoing burn debridement surgery?
• Does the surgical intervention worsen EoT, leading to increased postoperative syndecan 1 (sdc 1) levels compared to preoperative levels? Participants will:
• Undergo debridement surgery where the total area of debrided and donor sites covers 20% or more of the Total Body Surface Area (TBSA).
• Have their sdc 1 levels measured before and after surgery.
• Have perioperative factors analyzed to assess their impact on endothelial damage and glycocalyx functionality. This study aims to provide insight into how surgical resuscitation affects the endothelial glycocalyx in severely burned patients.

Conditions

Syndecan 1; Severe Burn; Endotheliopathy of Trauma; Endothelial Glycocalyx; Hemorrhagic Shock; Postoperative Complications

Keywords

Syndecan 1; Endotheliopathy; Glycocalyx; Proteoglycan; Severe burn

Outcome Measures

Primary Outcomes (1)

• Sdc-1 perioperative changes

  Sdc-1 levels will be measured upon admission to our Burn Unit, 24 hours after admission, on the 5th day of admission if surgery has not yet been performed, immediately before debridement surgery, and during the first 48 hours postoperatively.

  From admission to our Burn Unit until 48 hours post-debridement surgery.

Secondary Outcomes (6)

• Postoperative complications

  A) Immediate complications: 24 hours postoperatively; B) Early complications: 7 days postoperatively; C) Late complications: 30 days postoperatively

• Fluid and transfusion requirements

  During the surgical procedure and the first 48 hours postoperatively.

• Coagulation abnormalities (preoperative and postoperative)

  Preoperative (from admission to surgery) and postoperative (up to 48 hours after surgery).

• Duration of Mechanical Ventilation

  From the end of surgery until extubation, assessed over a period of up to 180 days.

• Length of Stay in the Intensive Care Unit (ICU)

  From admission to the ICU, after de debridement surgery, until discharge from the ICU (assessed over a period of up to 180 days).

Other Outcomes (2)

• Inhalation injury

  At admission

• Preoperative complications

  From admission to the Burn Unit until the day of the first debridement surgery, assessed over a period of up to 30 days following admission.

Study Arms (1)

Severe burn patients

Adult severely burned patients (TBSA ≥ 20%) undergoing debridement surgery.

Procedure: Debridement Surgery; Diagnostic Test: Sdc-1 Level Measurement

Interventions

Debridement Surgery PROCEDURE

Surgical debridement of burn wounds involving ≥ 20% of the TBSA, including debrided and donor sites.

Severe burn patients

Sdc-1 Level Measurement DIAGNOSTIC_TEST

Measurement of plasma sdc-1 levels in different situations to assess endothelial glycocalyx damage using an enzyme-linked immunosorbent assay (ELISA): Preoperatively: * Upon admission to the Burn Unit. * 24 hours after admission to the Burn Unit. * Prior to the start of surgery, after anesthetic induction. * If surgery is performed after the fifth day following the burn, an additional sdc-1 measurement will be taken on the fifth day of hospital admission. Postoperatively: * 6 hours after surgery. * 24 hours after surgery. * 48 hours after surgery.

Severe burn patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the Burn Unit of Vall d'Hebron University Hospital with burned TBSA ≥ 20% who undergo debridement surgery (total area between the debrided and donor sites ≥ 20% of TBSA).

You may qualify if:

• Patients over 18 years old with burned TBSA greater than or equal to 20%.
• Patients who will undergo debridement of at least 20% of the burned TBSA (including the debrided area and the donor site).

You may not qualify if:

• Under 18 years old.
• Pregnant women.
• Patient refusal.
• Polytraumatized patients.
• Electrical or chemical burns.
• Patients with any of the following pre-burn conditions: complicated heart disease\*, renal disease on hemodialysis/hemofiltration or with Glomerular Filtration Rate (GFR) \< 30 ml/min/1.73m², and liver cirrhosis (Child A, B, and C).
• (\* Definition of complicated heart disease: decompensated heart failure (NYHA class IV), Left Ventricular Ejection Fractio \< 40%, or severe valvular disease).
• Patients with a history of chronic inflammatory diseases (autoimmune disease).
• Patients on chronic treatment with corticosteroids or immunosuppressants.
• Patients requiring reintervention for debridement surgery who have already been included in the study during their first surgery.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (1)

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035, Spain

RECRUITING

Related Publications (13)

• Keyloun JW, Le TD, Brummel-Ziedins KE, Mclawhorn MM, Bravo MC, Orfeo T, Johnson LS, Moffatt LT, Pusateri AE, Shupp JW; SYSCOT Study Group. Inhalation Injury Is Associated With Endotheliopathy and Abnormal Fibrinolytic Phenotypes in Burn Patients: A Cohort Study. J Burn Care Res. 2022 Mar 23;43(2):432-439. doi: 10.1093/jbcr/irab102.

  PMID: 34089618 BACKGROUND

• Keyloun JW, Le TD, Pusateri AE, Ball RL, Carney BC, Orfeo T, Brummel-Ziedins KE, Bravo MC, McLawhorn MM, Moffatt LT, Shupp JW; and the SYSCOT study group. Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients. Shock. 2021 Aug 1;56(2):237-244. doi: 10.1097/SHK.0000000000001709.

  PMID: 33394974 BACKGROUND

• Jammer I, Wickboldt N, Sander M, Smith A, Schultz MJ, Pelosi P, Leva B, Rhodes A, Hoeft A, Walder B, Chew MS, Pearse RM; European Society of Anaesthesiology (ESA) and the European Society of Intensive Care Medicine (ESICM); European Society of Anaesthesiology; European Society of Intensive Care Medicine. Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on perioperative outcome measures. Eur J Anaesthesiol. 2015 Feb;32(2):88-105. doi: 10.1097/EJA.0000000000000118.

  PMID: 25058504 BACKGROUND

• Luker JN, Vigiola Cruz M, Carney BC, Day A, Moffatt LT, Johnson LS, Shupp JW. Shedding of the endothelial glycocalyx is quantitatively proportional to burn injury severity. Ann Burns Fire Disasters. 2018 Mar 31;31(1):17-22.

  PMID: 30174566 BACKGROUND

• Osuka A, Kusuki H, Yoneda K, Matsuura H, Matsumoto H, Ogura H, Ueyama M. Glycocalyx Shedding is Enhanced by Age and Correlates with Increased Fluid Requirement in Patients with Major Burns. Shock. 2018 Jul;50(1):60-65. doi: 10.1097/SHK.0000000000001028.

  PMID: 29023362 BACKGROUND

• Welling H, Henriksen HH, Gonzalez-Rodriguez ER, Stensballe J, Huzar TF, Johansson PI, Wade CE. Endothelial glycocalyx shedding in patients with burns. Burns. 2020 Mar;46(2):386-393. doi: 10.1016/j.burns.2019.05.009. Epub 2019 Dec 20.

  PMID: 31866179 BACKGROUND

• Rodriguez EG, Ostrowski SR, Cardenas JC, Baer LA, Tomasek JS, Henriksen HH, Stensballe J, Cotton BA, Holcomb JB, Johansson PI, Wade CE. Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma. J Am Coll Surg. 2017 Sep;225(3):419-427. doi: 10.1016/j.jamcollsurg.2017.05.012. Epub 2017 Jun 1.

  PMID: 28579548 BACKGROUND

• Johansson PI, Stensballe J, Ostrowski SR. Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism. Crit Care. 2017 Feb 9;21(1):25. doi: 10.1186/s13054-017-1605-5.

  PMID: 28179016 BACKGROUND

• Tapking C, Hernekamp JF, Horter J, Kneser U, Haug V, Vogelpohl J, Schulte M, Kremer T, Hundeshagen G. Influence of burn severity on endothelial glycocalyx shedding following thermal trauma: A prospective observational study. Burns. 2021 May;47(3):621-627. doi: 10.1016/j.burns.2020.07.021. Epub 2020 Aug 5.

  PMID: 32839038 BACKGROUND

• Abdullah S, Karim M, Legendre M, Rodriguez L, Friedman J, Cotton-Betteridge A, Drury R, Packer J, Guidry C, Duchesne J, Taghavi S, Jackson-Weaver O. Hemorrhagic Shock and Resuscitation Causes Glycocalyx Shedding and Endothelial Oxidative Stress Preferentially in the Lung and Intestinal Vasculature. Shock. 2021 Nov 1;56(5):803-812. doi: 10.1097/SHK.0000000000001764.

  PMID: 34259440 BACKGROUND

• Bunch CM, Chang E, Moore EE, Moore HB, Kwaan HC, Miller JB, Al-Fadhl MD, Thomas AV, Zackariya N, Patel SS, Zackariya S, Haidar S, Patel B, McCurdy MT, Thomas SG, Zimmer D, Fulkerson D, Kim PY, Walsh MR, Hake D, Kedar A, Aboukhaled M, Walsh MM. SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock. Front Physiol. 2023 Feb 27;14:1094845. doi: 10.3389/fphys.2023.1094845. eCollection 2023.

  PMID: 36923287 BACKGROUND

• Basas VA, Schutzman LM, Brown IE. Implications of the Regulation of Endothelial Glycocalyx Breakdown and Reconstitution in Severe Burn Injury. J Surg Res. 2023 Jun;286:110-117. doi: 10.1016/j.jss.2022.12.033. Epub 2023 Feb 17.

  PMID: 36804690 BACKGROUND

• Vigiola Cruz M, Carney BC, Luker JN, Monger KW, Vazquez JS, Moffatt LT, Johnson LS, Shupp JW. Plasma Ameliorates Endothelial Dysfunction in Burn Injury. J Surg Res. 2019 Jan;233:459-466. doi: 10.1016/j.jss.2018.08.027. Epub 2018 Sep 22.

  PMID: 30502286 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

All blood samples will be properly labeled with each patient's identification and sent to the central laboratory of our hospital, where they will be centrifuged and stored at -80ºC. Sample processing will be conducted once all patients have been recruited. The analysis of syndecan-1 will be performed using an enzyme-linked immunosorbent assay (ELISA). Each blood draw will consist of 10 ml. No DNA analysis will be conducted at any point; only syndecan-1 levels will be measured

MeSH Terms

Conditions

Burns; Shock, Hemorrhagic; Postoperative Complications

Condition Hierarchy (Ancestors)

Wounds and Injuries; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Central Study Contacts

Laura Pons Pellicé, MD

CONTACT

+34 626498575; laura.pons@vallhebron.cat

Luis Abarca Vilchez, MD, PhD

CONTACT

+34 661968807; luis.abarca@vallhebron.cat

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: November 1, 2024
• Study Start: March 5, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The IPD and supporting information will be available starting 6 months after the final study results are published and will remain available for 5 years.
• Access Criteria: Qualified researchers affiliated with academic, medical, or scientific institutions will be able to access the IPD and supporting information. They will be able to access de-identified individual participant data, including demographic information, clinical data, and outcome measures. Researchers can request access to the data by submitting a data-sharing proposal to Vall d'Hebron University Hospital and signing a data use agreement. Requests will be evaluated on a case-by-case basis.

Locations

ES (1)