Acute Respiratory FailurePhase 2VETtiPAT-ARFNCT05540834
Viscoelastic Testing Guided Tissue Plasminogen Activator Treatment in Acute Respiratory Failure
A Phase 2 study testing Alteplase in people with Acute Respiratory Failure and Hypercoagulability, run by South West Sydney Local Health District at 1 site in Australia.
Trial summary
Patients with coronavirus disease (COVID) and non-COVID acute respiratory failure (ARF) may be at an increased risk of thrombosis due to increased clot formation and decreased clot lysis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Respiratory Failure, Hypercoagulability, Fibrinolysis Shutdown
- What is being tested?
- Alteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteAustralia
- Study dates
- 18 May 2022to 1 Dec 2026
- Phase
- Phase 2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute respiratory failure of primary pulmonary infectious or extrapulmonary infectious aetiology with severity graded by the arterial oxygen partial pressure to inspired fraction of oxygen ratio (P/F) as per the Berlin definition: acute onset of hypoxemia with an arterial partial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2) ratio of less than or equal to 300 mmHg with positive end expiratory pressure (PEEP) of 5 cm of water (H2O) or greater
- Requiring admission to Intensive Care
- Aged 18 - 75 years of age
- Procoagulant profile on ClotPro (TradeMark) fibrinogen (FIB)-test +/- extrinsic coagulation pathway (EX)-test - above normal range for amplitude at 10 minutes (A10) and/or maximal clot firmness (MCF) at 30 minutes run time
- Lysis Time on ClotPro tissue plasminogen activator (TPA)-test ClotPro equal to or greater than 365 seconds
Who cannot join
- Platelet count <150 x 109/L or a reduction in platelet count of 50% or more in the last 24 hours
- Body weight < 60 kg
- Structural intracranial disease e.g. arterio-venous malformation or aneurysm
- Previous intracranial haemorrhage
- Ischaemic stroke within 3 months
- Traumatic cardiopulmonary resuscitation
Show all 20Show fewer
- Hypoxaemia from traumatic lung injury
- Active or recent bleeding
- Recent surgery, trauma or invasive procedure
- Systolic blood pressure (BP) > 180 mm Hg
- Diastolic BP > 100 mm Hg
- Pericarditis or pericardial fluid
- Diabetic retinopathy
- Currently menstruating
- Pregnancy - (beta-human chorionic gonadotropin (HCG) to be performed if of child-bearing age)
- Liver failure (known severe liver disease or an alanine aminotransferase or an aspartate aminotransferase level that is 5 times the upper limit of normal)
- Kidney failure (estimated Glomerular Filtration Rate (eGFR =<30 mL/hr or receiving renal replacement therapy)
- Use of therapeutic anticoagulation or platelet antagonists
- Not for active treatment
- Unlikely to survive until the day after tomorrow
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District
Liverpool, New South Wales, 1871
Anders Aneman, MD, PhD, +61 2 8738 3400, anders.aneman@swsahs.nsw.gov.au
About this study
Official title: A Phase 2 Safety, Dose-finding and Efficacy Study Evaluating Viscoelastic Testing (VET) Guided Tissue Plasminogen Activator (tPA) Treatment in Critically-ill Pro-thrombotic Acute Respiratory Failure
Patients with coronavirus disease (COVID) and non-COVID acute respiratory failure (ARF) may be at an increased risk of thrombosis due to increased clot formation and decreased clot lysis. This two stage study aims to utilise bedside coagulation technology to detect patients at increased risk and guide tPA treatment to maximise efficacy and safety through a personalised approach.
Read the detailed description
Acute respiratory failure (ARF) due to COVID is associated with an increased risk of thrombosis causing death. Therapeutic heparin administration was not beneficial in the critically ill.
In non-COVID ARF patients, the presence of multiple pulmonary vessel filling defects associated with the severity of disease and patient outcome, and resolved following the administration of the fibrinolytics, streptokinase and urokinase. An early phase I study reported improved oxygenation in patients with severe ARF following administration of plasminogen activators. The rationale for fibrinolytics in ARF has been published previously and is supported by meta-analysis of preclinical studies.
In both non-COVID and COVID associated ARF, defective fibrinolysis has been demonstrated. Standard coagulation tests cannot identify a hypercoagulable state nor assess fibrinolysis whereas viscoelastic testing (VET), a rapid, point-of-care device commonly used in Intensive Care, is able to detect these disorders. Numerous studies have demonstrated that VET is sufficiently sensitive to detect the coagulopathies associated with ARF, with several parameters associating with disease severity.
The VETtiPAT ARF trial uses VET to identify ARF patients with a procoagulant and hypofibrinolytic phenotype, then to guide tPA (Alteplase) administration thus maximising efficacy and safety through a personalised precision medicine approach.
- Being tested
- Alteplase
- Medical subject headings
- Thrombophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlteplaseDrug
Also called Tissue plasminogen activator, tPA, Actilyse, Activase
The enzyme tissue plasminogen activator that cleaves plasminogen to form plasmin.
| Study group | Role | What they receive |
|---|---|---|
| VET guided tPA administration + standard care | Experimental | Actilyse (tPA) will be administered as a 2-hour bolus then low dose infusion over 24 hours (safety and dose-finding stage) and 72 hours (randomised stage). Regular monitoring of the coagulation status and lysis time using VET will enable increases or decreases/cessation of the dose. Prophylactic low molecular weight heparin will continue throughout. Receives: Drug: Alteplase |
| Standard care | No intervention | Patients will receive standard care for their condition including prophylactic low molecular weight heparin. Coagulation status and lysis time monitoring with VET will occur at the same times as the experimental arm. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in clot lysis time on viscoelastic testing from baseline and up to 72 hours
The impact of alteplase administration on the clot lysis time (in seconds) measured by the TPA-test using the ClotPro at the bedside
Measured: From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls
Secondary outcomes (5)
Change in VET coagulation parameters from baseline and up to 72 hours
The impact of alteplase administration on clot formation related to fibrinogen and the extrinsic pathway (maximum clot firmness (MCF) / amplitude at 10 minutes (A10) in millimeters) measured by the FIB-test and EX-test using the ClotPro at the bedside
Measured: From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls
Changes in oxygenation
Arterial partial pressure of oxygen to inspired fraction of oxygen (P/F) ratio
Measured: From start to end of alteplase infusion/ equivalent timeframe in controls
Rate of participants with bleeding events
Any bleeding events Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater
Measured: From study entry to Day 5
Rate of thromboembolic events
Any thromboembolic event
Measured: From study entry to Day 30 or hospital discharge, whichever occurs first
Changes in organ function
Sequential Organ Failure Assessment (SOFA) score from 0 (normal) to a range of 1-4 with higher scores indicating more severe organ dysfunction
Measured: From start to end of alteplase infusion/ equivalent timeframe in controls
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2022
- Study start18 May 2022
- Primary completion1 May 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory FailureStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A two stage study evaluating (1) safety and dose-finding of escalating Actilyse (tPA) doses, followed by (2) a randomised, controlled efficacy study of VET-guided Actilyse treatment + standard care VERSUS standard care alone.
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- South West Sydney Local Health District
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anders Aneman, South West Sydney Local Health District
- Investigators
- Anders Aneman, Principal investigator, Sydney WAHS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05540834
- Sponsor's protocol ID
- ICU001
- Acronym
- VETtiPAT-ARF
- Status last verified
- Apr 2024
- First submitted
- 22 Aug 2022
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 36765421
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Safety, Dose-finding and Efficacy Study Evaluating Viscoelastic Testing (VET) Guided Tissue Plasminogen Activator (tPA) Treatment in Critically-ill Pro-thrombotic Acute Respiratory Failure
- ClinicalTrials.gov ID
- NCT05540834
- Acronym / sponsor ID
- VETtiPAT-ARF / ICU001
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- South West Sydney Local Health DistrictUniversity, hospital or other
- Study start
- 18 May 2022 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 15 Sep 2022 (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.
Patients with coronavirus disease (COVID) and non-COVID acute respiratory failure (ARF) may be at an increased risk of thrombosis due to increased clot formation and decreased clot lysis. This two stage study aims to utilise bedside coagulation technology to detect patients at increased risk and guide tPA treatment to maximise efficacy and safety through a personalised approach.
Detailed description
Acute respiratory failure (ARF) due to COVID is associated with an increased risk of thrombosis causing death. Therapeutic heparin administration was not beneficial in the critically ill.
In non-COVID ARF patients, the presence of multiple pulmonary vessel filling defects associated with the severity of disease and patient outcome, and resolved following the administration of the fibrinolytics, streptokinase and urokinase. An early phase I study reported improved oxygenation in patients with severe ARF following administration of plasminogen activators. The rationale for fibrinolytics in ARF has been published previously and is supported by meta-analysis of preclinical studies.
In both non-COVID and COVID associated ARF, defective fibrinolysis has been demonstrated. Standard coagulation tests cannot identify a hypercoagulable state nor assess fibrinolysis whereas viscoelastic testing (VET), a rapid, point-of-care device commonly used in Intensive Care, is able to detect these disorders. Numerous studies have demonstrated that VET is sufficiently sensitive to detect the coagulopathies associated with ARF, with several parameters associating with disease severity.
The VETtiPAT ARF trial uses VET to identify ARF patients with a procoagulant and hypofibrinolytic phenotype, then to guide tPA (Alteplase) administration thus maximising efficacy and safety through a personalised precision medicine approach.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A two stage study evaluating (1) safety and dose-finding of escalating Actilyse (tPA) doses, followed by (2) a randomised, controlled efficacy study of VET-guided Actilyse treatment + standard care VERSUS standard care alone.
| Arm | Type | Receives |
|---|---|---|
| VET guided tPA administration + standard care | Experimental | Drug: AlteplaseActilyse (tPA) will be administered as a 2-hour bolus then low dose infusion over 24 hours (safety and dose-finding stage) and 72 hours (randomised stage). Regular monitoring of the coagulation status and lysis time using VET will enable increases or decreases/cessation of the dose. Prophylactic low molecular weight heparin will continue throughout. |
| Standard care | No intervention | –Patients will receive standard care for their condition including prophylactic low molecular weight heparin. Coagulation status and lysis time monitoring with VET will occur at the same times as the experimental arm. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Acute respiratory failure of primary pulmonary infectious or extrapulmonary infectious aetiology with severity graded by the arterial oxygen partial pressure to inspired fraction of oxygen ratio (P/F) as per the Berlin definition: acute onset of hypoxemia with an arterial partial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2) ratio of less than or equal to 300 mmHg with positive end expiratory pressure (PEEP) of 5 cm of water (H2O) or greater
- Requiring admission to Intensive Care
- Aged 18 - 75 years of age
- Procoagulant profile on ClotPro (TradeMark) fibrinogen (FIB)-test +/- extrinsic coagulation pathway (EX)-test - above normal range for amplitude at 10 minutes (A10) and/or maximal clot firmness (MCF) at 30 minutes run time
- Lysis Time on ClotPro tissue plasminogen activator (TPA)-test ClotPro equal to or greater than 365 seconds
Key exclusion criteria (20 listed)
- Platelet count <150 x 109/L or a reduction in platelet count of 50% or more in the last 24 hours
- Body weight < 60 kg
- Structural intracranial disease e.g. arterio-venous malformation or aneurysm
- Previous intracranial haemorrhage
- Ischaemic stroke within 3 months
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 |
|---|---|---|
| AlteplaseAlso: Tissue plasminogen activator, tPA, Actilyse, ActivaseThe enzyme tissue plasminogen activator that cleaves plasminogen to form plasmin. | Drug | VET guided tPA administration + standard care |
Primary outcome
Change in clot lysis time on viscoelastic testing from baseline and up to 72 hours
Time frame: From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls
The impact of alteplase administration on the clot lysis time (in seconds) measured by the TPA-test using the ClotPro at the bedside
5 secondary outcomes
Change in VET coagulation parameters from baseline and up to 72 hours
Time frame: From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls
Changes in oxygenation
Time frame: From start to end of alteplase infusion/ equivalent timeframe in controls
Rate of participants with bleeding events
Time frame: From study entry to Day 5
Rate of thromboembolic events
Time frame: From study entry to Day 30 or hospital discharge, whichever occurs first
Changes in organ function
Time frame: From start to end of alteplase infusion/ equivalent timeframe in controls
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 17 Apr 2024.
- Derived from this study: 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.
- Individual participant dataSharing planned: No
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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.
Anders Aneman principal investigator
Sydney WAHS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alteplase in people with Acute Respiratory Failure and Hypercoagulability, run by South West Sydney Local Health District at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. 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 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 (+61 427915693, 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?
Change in clot lysis time on viscoelastic testing from baseline and up to 72 hours (time frame: From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls). 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 NCT05540834, which also lists 1 linked publication.
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 17 Apr 2024.