Fibrinolysis Resistance in Infection and Trauma

NCT ID: NCT06680180

Last Updated: 2024-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-06-01

Study Completion Date

2026-06-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Sepsis and Septic Shock Trauma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Viscoelastometric assessment of fibrinolysis

Intervention Type DIAGNOSTIC_TEST

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

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.

Viscoelastometric assessment of fibrinolysis

Intervention Type DIAGNOSTIC_TEST

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Viscoelastometric assessment of fibrinolysis

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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


* 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

Exclusion Criteria

* On oral anticoagulant/antiplatelet therapy
* Not for full, active ICU support
* Death is deemed inevitable within 24 hrs


* Nursing home resident
* Unsurvivable head injury
* Not for full, active ICU support
* Death is deemed inevitable within 24 hrs
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Liverpool Hospital, South Western Sydney Local Health District

UNKNOWN

Sponsor Role collaborator

The Canberra Hospital

OTHER

Sponsor Role collaborator

Royal North Shore Hospital

OTHER

Sponsor Role collaborator

Macquarie University, Australia

OTHER

Sponsor Role collaborator

Anders Aneman

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Anders Aneman

Conjoint Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The Canberra hospital (ICU)

Canberra, Australian Capital Territory, Australia

Site Status RECRUITING

Liverpool Hospital (ICU)

Liverpool, New South Wales, Australia

Site Status RECRUITING

Macquarie University Hospital (ICU)

Macquarie, New South Wales, Australia

Site Status RECRUITING

Royal North Shore Hospital (ICU)

St Leonards, New South Wales, Australia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Australia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Anders Aneman, MD, PhD, EDIC, FCICM

Role: CONTACT

+61427915693

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

Role: CONTACT

+61419723330

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Philip Crispin, MBBS(Hons), FRACP, FRCPA

Role: primary

+ 61251240000

Sean W Chan

Role: backup

+ 61251240000

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

Role: primary

+ 61419723330

Eurwin Suryana, BMedSci (hons), PhD

Role: backup

+ 61415148742

Anders Aneman, MD, PhD, EDIC, FCICM

Role: primary

+ 61427915693

Pierre Janin

Role: primary

+ 61299267111

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 36765421 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2022/ETH02122

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.