Using viscoelastic testing to guide tPA treatment for acute respiratory failure

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

This study is testing if using a special blood test can help doctors decide when to give a treatment for blood clots to patients with acute respiratory failure, including those with COVID-19.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: South West Sydney Local Health District (Academic / other)
• Locations: 1 site (Liverpool, New South Wales)
• Trial ID: NCT05540834 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to improve treatment for patients experiencing acute respiratory failure (ARF) by utilizing viscoelastic testing (VET) to identify those at increased risk of thrombosis. The study focuses on both COVID and non-COVID related ARF, where patients often exhibit a hypercoagulable state and impaired fibrinolysis. By guiding the administration of tissue plasminogen activator (tPA) based on VET results, the trial seeks to personalize treatment to enhance efficacy and safety. The approach is designed to address the limitations of standard coagulation tests and provide a more accurate assessment of coagulation status in critically ill patients.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with acute respiratory failure requiring intensive care, exhibiting a procoagulant profile.

Not a fit: Patients with a platelet count below 150 x 10^9/L or significant reductions in platelet count may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve outcomes for patients with acute respiratory failure by reducing the risk of thrombosis and enhancing recovery.

How similar studies have performed: Previous studies have shown promise in using fibrinolytics for ARF, but this specific approach utilizing viscoelastic testing is novel.

Eligibility criteria

Inclusion Criteria:

1. 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
2. Requiring admission to Intensive Care
3. Aged 18 - 75 years of age
4. 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
5. Lysis Time on ClotPro tissue plasminogen activator (TPA)-test ClotPro equal to or greater than 365 seconds

Exclusion Criteria:

1. Platelet count \<150 x 109/L or a reduction in platelet count of 50% or more in the last 24 hours
2. Body weight \< 60 kg
3. Structural intracranial disease e.g. arterio-venous malformation or aneurysm
4. Previous intracranial haemorrhage
5. Ischaemic stroke within 3 months
6. Traumatic cardiopulmonary resuscitation
7. Hypoxaemia from traumatic lung injury
8. Active or recent bleeding
9. Recent surgery, trauma or invasive procedure
10. Systolic blood pressure (BP) \> 180 mm Hg
11. Diastolic BP \> 100 mm Hg
12. Pericarditis or pericardial fluid
13. Diabetic retinopathy
14. Currently menstruating
15. Pregnancy - (beta-human chorionic gonadotropin (HCG) to be performed if of child-bearing age)
16. Liver failure (known severe liver disease or an alanine aminotransferase or an aspartate aminotransferase level that is 5 times the upper limit of normal)
17. Kidney failure (estimated Glomerular Filtration Rate (eGFR =\<30 mL/hr or receiving renal replacement therapy)
18. Use of therapeutic anticoagulation or platelet antagonists
19. Not for active treatment
20. Unlikely to survive until the day after tomorrow

Where this trial is running

Liverpool, New South Wales

• Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District — Liverpool, New South Wales, Australia (Recruiting)

Study contacts

• Principal investigator: Anders Aneman — Sydney WAHS
• Study coordinator: Anders Aneman

Conditions Acute Respiratory Failure; Hypercoagulability; Fibrinolysis Shutdown