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

ICU001

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.

2022-05-18

2026-05-01

2026-12-01

Recruiting

Early phase I

70

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 70, 'type': 'ESTIMATED'}}

2024-04-17