Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05540834
Other study ID # ICU001
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date May 18, 2022
Est. completion date December 1, 2026

Study information

Verified date April 2024
Source South West Sydney Local Health District
Contact Anders Aneman
Phone +61 427915693
Email Anders.Aneman@health.nsw.gov.au
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 70
Est. completion date December 1, 2026
Est. primary completion date May 1, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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

Study Design


Intervention

Drug:
Alteplase
The enzyme tissue plasminogen activator that cleaves plasminogen to form plasmin.

Locations

Country Name City State
Australia Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District Liverpool New South Wales

Sponsors (1)

Lead Sponsor Collaborator
South West Sydney Local Health District

Country where clinical trial is conducted

Australia, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls
Secondary 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 From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls
Secondary Changes in oxygenation Arterial partial pressure of oxygen to inspired fraction of oxygen (P/F) ratio From start to end of alteplase infusion/ equivalent timeframe in controls
Secondary Rate of participants with bleeding events Any bleeding events Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater From study entry to Day 5
Secondary Rate of thromboembolic events Any thromboembolic event From study entry to Day 30 or hospital discharge, whichever occurs first
Secondary 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 From start to end of alteplase infusion/ equivalent timeframe in controls
See also
  Status Clinical Trial Phase
Recruiting NCT05144633 - Blue Protocol and Eko Artificial Intelligence Are Best (BEA-BEST)
Completed NCT04534569 - Expert Panel Statement for the Respiratory Management of COVID-19 Related Acute Respiratory Failure (C-ARF)
Recruiting NCT03021902 - Nutrition and Exercise in Critical Illness Phase 2
Completed NCT02902146 - Bougie Use in Emergency Airway Management N/A
Completed NCT02901158 - Esophageal Manometry in Mechanically Ventilated Patients
Completed NCT02236559 - High Flow Therapy for the Treatment of Respiratory Failure in the ED N/A
Recruiting NCT02056093 - Comparison of Proportional Assist Ventilation And Neurally Adjusted Ventilator Assist N/A
Terminated NCT01083277 - Variable Ventilation During Acute Respiratory Failure N/A
Not yet recruiting NCT01668368 - Goal Directed Mechanical Ventilation Aimed at Optimal Lung Compliance N/A
Completed NCT01462279 - Effect of Thiamine on Oxygen Utilization (VO2) in Critical Illness N/A
Completed NCT01114022 - Prevention Inhalation of Bacterial by Using Endotracheal Tube Balloon Polyvinyl Chloride or Polyurethane N/A
Active, not recruiting NCT01058421 - Treatment of Critical Illness Polyneuromyopathy Phase 2
Completed NCT00252616 - Timing of Target Enteral Feeding in the Mechanically Ventilated Patient Phase 2/Phase 3
Recruiting NCT04098094 - Outcomes of RV Dysfunction in Acute Exacerbation of Chronic Respiratory Diseases
Recruiting NCT06051292 - Decremental Esophageal Catheter Filling Volume Titration For Transpulmonary Pressure Measurement N/A
Completed NCT04601090 - Survival Rates and Longterm Outcomes After COVID-19
Recruiting NCT05423301 - Global Physiotherapy in ICU Patients With High Risk Extubation Failure N/A
Completed NCT02447692 - Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study N/A
Completed NCT04016480 - HFNC During Bronchoscopy for Bronchoalveolar Lavage N/A
Completed NCT04507425 - High Flow Nasal Cannula With Noninvasive Ventilation N/A