Sepsis and Septic ShockFORTITUDENCT06680180
Fibrinolysis Resistance in Infection and Trauma
An observational study of Sepsis and Septic Shock and Trauma, run by Anders Aneman at 4 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sepsis and Septic Shock, Trauma
- What is being tested?
- Viscoelastometric assessment of fibrinolysis
- Type of treatment
- Pill or oral medicine
- How many people
- 150 participants
- Where
- 4 sitesAustralia
- Study dates
- 1 Jun 2024to 1 Jun 2026
- How long will I take part?
- 15 Days
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients who are admitted to an ICU
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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Australia4 sites, 4 recruiting
- Recruiting
The Canberra hospital (ICU)
Canberra, Australian Capital Territory, 2605
Philip Crispin, MBBS(Hons), FRACP, FRCPA, + 61251240000, philip.crispin@act.gov.au
Sean W Chan, + 61251240000, seanweng.chan@act.gov.au
- Recruiting
Liverpool Hospital (ICU)
Liverpool, New South Wales, 2170
Lucy Coupland, Nurs Cert, BSci (hons), PhD, + 61419723330, lucy.coupland@health.nsw.gov.au
Eurwin Suryana, BMedSci (hons), PhD, + 61415148742, eurwin.suryana@health.nsw.gov.au
- Recruiting
Macquarie University Hospital (ICU)
Macquarie, New South Wales, 2109
Anders Aneman, MD, PhD, EDIC, FCICM, + 61427915693, anders.aneman@health.nsw.gov.au
- Recruiting
Royal North Shore Hospital (ICU)
St Leonards, New South Wales, 2065
Pierre Janin, + 61299267111, pierre.janin@health.nsw.gov.au
About this study
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.
Read the 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.
- Conditions
- Sepsis and Septic Shock, Trauma
- Being tested
- Viscoelastometric assessment of fibrinolysis
- Keywords
- Viscoelastic testing (VET), Sepsis, Trauma, Fibrinolytic Agents, Fibrin Modulating Agents, Tissue Plasminogen Activator, Plasminogen
- Medical subject headings
- Sepsis, Shock, Septic, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Viscoelastometric assessment of fibrinolysisDiagnostic test
Viscoelastometric assessment of whole blood fibrinolysis using supplemental tissue plasminogen activator (tPA) and other agents ex vivo to influence fibrinolysis capacity.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: Viscoelastometric assessment of fibrinolysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
VET testing and analysis
VET testing in whole blood will determine the kinetics and contribution of:
- 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.
Measured: 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.
Measured: From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2024
- Study start1 Jun 2024
- Primary completion31 Dec 2025 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sepsis and Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
- Target duration
- 15 Days
Sponsor and investigators
- Lead sponsor
- Anders Aneman
- Sponsor type
- University, hospital or other
- Collaborators
- Liverpool Hospital, South Western Sydney Local Health District, The Canberra Hospital, Royal North Shore Hospital, Macquarie University, Australia
- Responsible party
- Sponsor-investigator, Anders Aneman, South West Sydney Local Health District
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06680180
- Sponsor's protocol ID
- 2022/ETH02122
- Acronym
- FORTITUDE
- Status last verified
- Nov 2024
- First submitted
- 9 Oct 2024
- Last updated
- 8 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36765421Coupland LA, Richardson M, Suryana E, Olechnowicz S, Self M, Motyer A, Bowden R, Aneman A. Investigating Fibrinolysis Resistance in Sepsis Using High-Multiplex Plasma Proteomics: A Statistical Analysis Plan. Acta Anaesthesiol Scand. 2026 Nov;70(10):e70358. doi: 10.1111/aas.70358.
PubMed 42885115
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibrinolysis Resistance in Infection and Trauma
- ClinicalTrials.gov ID
- NCT06680180
- Acronym / sponsor ID
- FORTITUDE / 2022/ETH02122
- Conditions
- Sepsis and Septic Shock, Trauma
- Keywords
- Viscoelastic testing (VET), Sepsis, Trauma, Fibrinolytic Agents, Fibrin Modulating Agents, Tissue Plasminogen Activator, Plasminogen
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Anders AnemanUniversity, hospital or other
- Collaborators
- Liverpool Hospital, South Western Sydney Local Health District, The Canberra Hospital, Royal North Shore Hospital, Macquarie University, Australia
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 8 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 15 Days
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sepsis/Septic shock | – | Diagnostic Test: Viscoelastometric assessment of fibrinolysisAccording 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. |
| Severe Trauma | – | Diagnostic Test: Viscoelastometric assessment of fibrinolysisAdmitted 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who are admitted to an ICU
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Viscoelastometric assessment of fibrinolysisViscoelastometric assessment of whole blood fibrinolysis using supplemental tissue plasminogen activator (tPA) and other agents ex vivo to influence fibrinolysis capacity. | Diagnostic test | Sepsis/Septic shock, Severe Trauma |
Primary outcome
VET testing and analysis
Time frame: From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission
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.
Laboratory evaluation of fibrinolytic profile
Time frame: From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2024.
- Background: PubMed 36765421Coupland 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.
- Derived from this study: PubMed 42885115Coupland LA, Richardson M, Suryana E, Olechnowicz S, Self M, Motyer A, Bowden R, Aneman A. Investigating Fibrinolysis Resistance in Sepsis Using High-Multiplex Plasma Proteomics: A Statistical Analysis Plan. Acta Anaesthesiol Scand. 2026 Nov;70(10):e70358. doi: 10.1111/aas.70358.
- Individual participant dataSharing planned: No
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Septic Shock and Trauma, run by Anders Aneman at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anders Aneman, MD, PhD, EDIC, FCICM (+61427915693, anders.aneman@health.nsw.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VET testing and analysis (time frame: From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06680180, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2024.