Clinical trial NCT06680180: Fibrinolysis Resistance in Infection and Trauma
Official title: Fibrinolysis Resistance in Infection and Trauma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sepsis and Septic Shock
Trauma
Keywords: Viscoelastic testing (VET)
Sepsis
Trauma
Fibrinolytic Agents
Fibrin Modulating Agents
Tissue Plasminogen Activator
Plasminogen
Lead sponsor: South West Sydney Local Health District
Sponsor class: OTHER
Collaborators: name: Liverpool Hospital, South Western Sydney Local Health District
name: The Canberra Hospital
name: Royal North Shore Hospital
name: Macquarie University, Australia
First posted: 2024-11-08
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who are admitted to an ICU

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.

Detailed 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.

Eligibility criteria: Sepsis/Septic shock Inclusion Criteria:

* 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

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 transfusion within 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

Primary outcomes:
measure: VET testing and analysis
timeFrame: From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission
measure: Laboratory evaluation of fibrinolytic profile
timeFrame: From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission
Secondary outcomes:
Other outcomes:
Locations:
city: Canberra
country: Australia
facility: The Canberra hospital (ICU)
state: Australian Capital Territory
city: Liverpool
country: Australia
facility: Liverpool Hospital (ICU)
state: New South Wales
city: Macquarie
country: Australia
facility: Macquarie University Hospital (ICU)
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital (ICU)
state: New South Wales
Study officials:
References:
citation: 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.