Fibrinolysis Resistance in Infection and Trauma

NCT06680180 | Recruiting

• 1 other identifier: 2022/ETH02122
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 4

Brief Summary

Blood coagulation disorders are often seen in critically ill patients e.g. with severe infection or following extensive injury, that can lead to life threatening events as a result of excessive blood clot formation leading to organ failure. This study aims to use Viscoelastic Testing (VET) technology to detect patients at risk of excessive blood blot formation at the bedside, test new blood coagulation drugs, and guide life-saving use of blood modifying treatments.

Conditions

Sepsis and Septic Shock; Trauma

Keywords

Viscoelastic testing (VET); Sepsis; Trauma; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen

Outcome Measures

Primary Outcomes (2)

• VET testing and analysis

  VET testing in whole blood will determine the kinetics and contribution of: i) both plasma and platelets to clot formation following the addition of tissue factor. ii) plasma clot formation only by adding tissue factor and platelet inhibitors. iii) tPA-induced fibrinolysis by adding tissue factor and tPA. The following test parameters will be used for analytical purposes: clotting time, clot amplitude at 10 min, maximum clot firmness, lysis time, maximum lysis. The platelet contribution to the clot will be calculated by subtracting (ii) from (i). An additional blood sample will be collected at the time of VET analysis for processing and storage for subsequent fibrinolysis protein analysis.

  From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission

• Laboratory evaluation of fibrinolytic profile

  We will evaluate the temporal changes in key fibrinolytic markers (i.e. plasminogen, antiplasmin, PAI-1 activity) and also changes in overall fibrinolytic capacity of patient plasma (i.e. how responsive plasma is to generate plasmin ex vivo) in relation to the VET testing. Commercial ELISAs will be used to determine plasminogen, alpha2 antiplasmin levels, PAI-1 and tPA activity; A novel tPA inducible plasmin-antiplasmin test will be used to evaluate plasmin generation; amidolytic assay will be used to determine plasmin activity.

  From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission

Study Arms (2)

Sepsis/Septic shock

According to Sepsis-3 definitions (including SARS CoV-2 as pathogen); expected to remain in ICU and survive beyond the day after tomorrow and for full, active ICU treatment; arterial and secure venous access established or imminent as part of standard care; not on oral anticoagulant/antiplatelet therapy.

Diagnostic Test: Viscoelastometric assessment of fibrinolysis

Severe Trauma

Admitted via the Emergency Department resuscitation bay requiring trauma team response; deemed at risk of significant blood loss and where transfusion of blood products i considered in the ED during the acute phase of the resuscitation by a senior clinician; expected to remain in ICH and survive beyond the day after tomorrow and for full, active ICU treatment; Not on oral anticoagulant/antiplatelet therapy. A clinical based inclusion approach is the most pragmatic means of patient selection and can be objectively supported by routine blood tests demonstrating poor oxygen supply to the organs. Exclusion criteria: unsurvivable head injury.

Diagnostic Test: Viscoelastometric assessment of fibrinolysis

Interventions

Viscoelastometric assessment of fibrinolysis DIAGNOSTIC_TEST

Viscoelastometric assessment of whole blood fibrinolysis using supplemental tissue plasminogen activator (tPA) and other agents ex vivo to influence fibrinolysis capacity.

Sepsis/Septic shock; Severe Trauma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who are admitted to an ICU

You may qualify if:

• Admission to ICU, needing at least one organ supportand principally for the management of clinically suspected Sepsis or Septic shock according to Spesis-3 criteria (including SARS-COV-2)
• Expected to remain in ICU and survive beyond the day after tomorrow

You may not qualify if:

• On oral anticoagulant/antiplatelet therapy
• Not for full, active ICU support
• Death is deemed inevitable within 24 hrs
• Trauma is the principal diagnosis on ICU admission
• Expected to remain in ICU and survive beyond the day after tomorrow
• Receiving respiratory support at the time of ICU admission - high-flow nasal prongs, non-invasive or invasive ventilation
• Already received, or considered at risk of needing a blood product transfusion within 24 hrs of injury
• Nursing home resident
• Unsurvivable head injury
• Not for full, active ICU support
• Death is deemed inevitable within 24 hrs

Sponsors & Collaborators

• Anders Aneman: lead
• Liverpool Hospital, South Western Sydney Local Health District: collaborator
• The Canberra Hospital: collaborator
• Royal North Shore Hospital: collaborator
• Macquarie University, Australia: collaborator

Study Sites (4)

The Canberra hospital (ICU)

Canberra, Australian Capital Territory, 2605, Australia

RECRUITING

Liverpool Hospital (ICU)

Liverpool, New South Wales, 2170, Australia

RECRUITING

Macquarie University Hospital (ICU)

Macquarie, New South Wales, 2109, Australia

RECRUITING

Royal North Shore Hospital (ICU)

St Leonards, New South Wales, 2065, Australia

RECRUITING

Related Publications (1)

• Coupland LA, Rabbolini DJ, Schoenecker JG, Crispin PJ, Miller JJ, Ghent T, Medcalf RL, Aneman AE. Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study. Crit Care. 2023 Feb 10;27(1):55. doi: 10.1186/s13054-023-04329-5.

  PMID: 36765421 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Sepsis; Shock, Septic; Wounds and Injuries

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Central Study Contacts

Anders Aneman, MD, PhD, EDIC, FCICM

CONTACT

+61427915693; anders.aneman@health.nsw.gov.au

Lucy Coupland, Nurs Cert, BSci (hons), PhD

CONTACT

+61419723330; lucy.coupland@health.nsw.gov.au

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 15 Days
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Conjoint Professor

Study Record Dates

• First Submitted: October 9, 2024
• First Posted: November 8, 2024
• Study Start: June 1, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 8, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)