Share

Save

Viscoelastic Testing Guided Tissue Plasminogen Activator Treatment in Acute Respiratory Failure

PHASE2RECRUITING

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.

info
Simpliy with AI

Study details:

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.

info
Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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
  • info
    Simplify with AI

    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2022-05-18

    Primary completion: 2026-05-01

    Study completion finish: 2026-12-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE2

    trial

    Trial ID

    NCT05540834

    Intervention or treatment

    DRUG: Alteplase

    Conditions

    • Acute Respiratory Failure
    • Hypercoagulability
    • Fibrinolysis Shutdown
    Image related to Acute Respiratory Failure
    • Condition: Acute Respiratory Failure, Hypercoagulability and more

    • DRUG: Alteplase

    • Liverpool, New South Wales, Australia

    • Sponsor: South West Sydney Local Health District

    Find a site

    Closest Location:

    Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District

    Research sites nearby

    Select from list below to view details:

    • Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District

      Liverpool, New South Wales, Australia

    Loading...

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: VET guided tPA administration + 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.
    DRUG: Alteplase
    • The enzyme tissue plasminogen activator that cleaves plasminogen to form plasmin.
    NO_INTERVENTION: Standard care
    • 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.
    Not specified

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Change in clot lysis time on viscoelastic testing from baseline and up to 72 hoursThe impact of alteplase administration on the clot lysis time (in seconds) measured by the TPA-test using the ClotPro at the bedsideFrom start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Change in VET coagulation parameters from baseline and up to 72 hoursThe 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 bedsideFrom start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls
    Changes in oxygenationArterial partial pressure of oxygen to inspired fraction of oxygen (P/F) ratioFrom start to end of alteplase infusion/ equivalent timeframe in controls
    Rate of participants with bleeding eventsAny bleeding events Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greaterFrom study entry to Day 5
    Rate of thromboembolic eventsAny thromboembolic eventFrom study entry to Day 30 or hospital discharge, whichever occurs first
    Changes in organ functionSequential Organ Failure Assessment (SOFA) score from 0 (normal) to a range of 1-4 with higher scores indicating more severe organ dysfunctionFrom start to end of alteplase infusion/ equivalent timeframe in controls

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

    No questions submitted. Be the first to ask a question!

    You may be eligible to participate in this trial based on your search.Apply for study
    Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

    References

    Clinical Trials Gov: Viscoelastic Testing Guided Tissue Plasminogen Activator Treatment in Acute Respiratory Failure

    Other trails to consider

    Top searched conditions