Viscoelastic Testing Guided Tissue Plasminogen Activator Treatment in Acute Respiratory Failure

NCT05540834 | Recruiting Phase 2 DMC

• 1 other identifier: ICU001
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Respiratory Failure; Hypercoagulability; Fibrinolysis Shutdown

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change in VET coagulation parameters from baseline and up to 72 hours

  From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls

• Changes in oxygenation

  From start to end of alteplase infusion/ equivalent timeframe in controls

• Rate of participants with bleeding events

  From study entry to Day 5

• Rate of thromboembolic events

  From study entry to Day 30 or hospital discharge, whichever occurs first

• Changes in organ function

  From start to end of alteplase infusion/ equivalent timeframe in controls

Study Arms (2)

VET guided tPA administration + standard care

EXPERIMENTAL

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

Standard care

NO INTERVENTION

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.

Interventions

Alteplase DRUG

The enzyme tissue plasminogen activator that cleaves plasminogen to form plasmin.

Also known as: Tissue plasminogen activator, tPA, Actilyse, Activase

VET guided tPA administration + standard care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• South West Sydney Local Health District: lead

Study Sites (1)

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

Liverpool, New South Wales, 1871, Australia

RECRUITING

Related Publications (1)

• Coupland LA, Rabbolini DJ, Schoenecker JG, Crispin PJ, Miller JJ, Ghent T, Medcalf RL, Aneman AE. Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study. Crit Care. 2023 Feb 10;27(1):55. doi: 10.1186/s13054-023-04329-5.

  PMID: 36765421 DERIVED

MeSH Terms

Conditions

Thrombophilia

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Anders Aneman

  Sydney WAHS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anders Aneman

CONTACT

+61 427915693; Anders.Aneman@health.nsw.gov.au

Lucy Coupland

CONTACT

+61 419723330; l.coupland@unsw.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: September 15, 2022
• Study Start: May 18, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)