Fibrinolysis Resistance in Infection and Trauma

Last updated: November 6, 2024
Sponsor: Anders Aneman
Overall Status: Active - Recruiting

Phase

N/A

Condition

Hyponatremia

Treatment

Viscoelastometric assessment of fibrinolysis

Clinical Study ID

NCT06680180
2022/ETH02122
  • Ages > 18
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Sepsis/Septic shock Inclusion Criteria:

  • Admission to ICU, needing at least one organ supportand principally for themanagement of clinically suspected Sepsis or Septic shock according to Spesis-3criteria (including SARS-COV-2)

  • Expected to remain in ICU and survive beyond the day after tomorrow

Exclusion

Sepsis Exclusion Criteria:

  • On oral anticoagulant/antiplatelet therapy

  • Not for full, active ICU support

  • Death is deemed inevitable within 24 hrs

Trauma Inclusion Criteria:

  • 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 transfusionwithin 24 hrs of injury

Trauma Exclusion Criteria:

  • Nursing home resident

  • Unsurvivable head injury

  • Not for full, active ICU support

  • Death is deemed inevitable within 24 hrs

Study Design

Total Participants: 150
Treatment Group(s): 1
Primary Treatment: Viscoelastometric assessment of fibrinolysis
Phase:
Study Start date:
June 01, 2024
Estimated Completion Date:
June 01, 2026

Study Description

In healthy individuals blood coagulates (clots) to minimise blood loss then, as part of the process of wound repair, blood clots are broken down in a process called fibrinolysis which involves two key proteins: tissue plasminogen activator (tPA) and plasminogen. In severe infection (sepsis) or following extensive injury (trauma), fibrinolysis abnormalities commonly develop, which include reduced fibrinolysis activity (fibrinolysis resistance) resulting in extensive clot formation and frequently leading to organ failure and death. Currently, the cause of fibrinolysis resistance in sepsis and trauma are unknown and clinical trials to address coagulopathies in sepsis have failed, likely due to inadequate disease phenotyping.

The viscoelastic testing (VET) technology ClotPro® has been used to identify fibrinolysis resistance in 55% of critically ill patients (COVID and non-COVID with acute respiratory failure) and through novel adaptation of the technology, determined that this is likely driven by reduced tPA and/or plasminogen activity. Furthermore, it has been used to detect in real time the impact of a 24 hr tPA infusion on fibrinolysis in a patient. Thus, this preliminary work has demonstrated the feasibility of a personalised treatment approach to fibrinolysis resistance management that can guide life-saving use of fibrinolysis enhancers to overcome resistance in an individualised basis that is likely to increase therapeutic efficacy and safety.

This project aims to scientifically validate the aforementioned preliminary work, increase our knowledge on the mechanisms of reduced fibrinolysis enzyme activity in severe infection and injury, discover potential treatment options, and progress these findings towards translation. The results of this project will drive future clinical trials of repurposed or novel therapies guided by VET to deliver a personalised dose to critically ill patients who demonstrate fibrinolysis resistance, which in conjunction with rapid detection, is anticipated to significantly improve patient outcomes.

Connect with a study center

  • The Canberra hospital (ICU)

    Canberra, Australian Capital Territory 2605
    Australia

    Active - Recruiting

  • Liverpool Hospital (ICU)

    Liverpool, New South Wales 2170
    Australia

    Active - Recruiting

  • Macquarie University Hospital (ICU)

    Macquarie, New South Wales 2109
    Australia

    Active - Recruiting

  • Royal North Shore Hospital (ICU)

    St Leonards, New South Wales 2065
    Australia

    Active - Recruiting

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