Viscoelastic Testing Guided Tissue Plasminogen Activator Treatment in Acute Respiratory Failure (VETtiPAT-ARF)
Acute Respiratory Failure, Hypercoagulability, Fibrinolysis Shutdown
About this trial
This is an interventional treatment trial for Acute Respiratory Failure
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health DistrictRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
No Intervention
VET guided tPA administration + standard care
Standard care
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.
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.