Ignite Creation Date:
2025-12-25 @ 2:30 AM
Ignite Modification Date:
2025-12-26 @ 1:05 AM
Study NCT ID:
NCT05540834
Status:
RECRUITING
Last Update Posted:
2024-04-17
First Post:
2022-08-22
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Viscoelastic Testing Guided Tissue Plasminogen Activator Treatment in Acute Respiratory Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019851', 'term': 'Thrombophilia'}], 'ancestors': [{'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D010959', 'term': 'Tissue Plasminogen Activator'}], 'ancestors': [{'id': 'D012697', 'term': 'Serine Endopeptidases'}, {'id': 'D010450', 'term': 'Endopeptidases'}, {'id': 'D010447', 'term': 'Peptide Hydrolases'}, {'id': 'D006867', 'term': 'Hydrolases'}, {'id': 'D004798', 'term': 'Enzymes'}, {'id': 'D045762', 'term': 'Enzymes and Coenzymes'}, {'id': 'D057057', 'term': 'Serine Proteases'}, {'id': 'D010960', 'term': 'Plasminogen Activators'}, {'id': 'D001779', 'term': 'Blood Coagulation Factors'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2022-09-01', 'size': 1237926, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-09-12T03:25', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', '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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 70}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-05-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2026-12-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-04-15', 'studyFirstSubmitDate': '2022-08-22', 'studyFirstSubmitQcDate': '2022-09-12', 'lastUpdatePostDateStruct': {'date': '2024-04-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-09-15', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-05-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in clot lysis time on viscoelastic testing from baseline and up to 72 hours', 'timeFrame': 'From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls', 'description': 'The impact of alteplase administration on the clot lysis time (in seconds) measured by the TPA-test using the ClotPro at the bedside'}], 'secondaryOutcomes': [{'measure': 'Change in VET coagulation parameters from baseline and up to 72 hours', 'timeFrame': 'From start to end of alteplase infusion + 1 and up to 72 hours later/ equivalent timeframe in controls', 'description': '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'}, {'measure': 'Changes in oxygenation', 'timeFrame': 'From start to end of alteplase infusion/ equivalent timeframe in controls', 'description': 'Arterial partial pressure of oxygen to inspired fraction of oxygen (P/F) ratio'}, {'measure': 'Rate of participants with bleeding events', 'timeFrame': 'From study entry to Day 5', 'description': 'Any bleeding events Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater'}, {'measure': 'Rate of thromboembolic events', 'timeFrame': 'From study entry to Day 30 or hospital discharge, whichever occurs first', 'description': 'Any thromboembolic event'}, {'measure': 'Changes in organ function', 'timeFrame': 'From start to end of alteplase infusion/ equivalent timeframe in controls', 'description': 'Sequential Organ Failure Assessment (SOFA) score from 0 (normal) to a range of 1-4 with higher scores indicating more severe organ dysfunction'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Acute Respiratory Failure', 'Hypercoagulability', 'Fibrinolysis Shutdown']}, 'referencesModule': {'references': [{'pmid': '36765421', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nIn 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.\n\nIn 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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. 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\n2. Requiring admission to Intensive Care\n3. Aged 18 - 75 years of age\n4. 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\n5. Lysis Time on ClotPro tissue plasminogen activator (TPA)-test ClotPro equal to or greater than 365 seconds\n\nExclusion Criteria:\n\n1. Platelet count \\<150 x 109/L or a reduction in platelet count of 50% or more in the last 24 hours\n2. Body weight \\< 60 kg\n3. Structural intracranial disease e.g. arterio-venous malformation or aneurysm\n4. Previous intracranial haemorrhage\n5. Ischaemic stroke within 3 months\n6. Traumatic cardiopulmonary resuscitation\n7. Hypoxaemia from traumatic lung injury\n8. Active or recent bleeding\n9. Recent surgery, trauma or invasive procedure\n10. Systolic blood pressure (BP) \\> 180 mm Hg\n11. Diastolic BP \\> 100 mm Hg\n12. Pericarditis or pericardial fluid\n13. Diabetic retinopathy\n14. Currently menstruating\n15. Pregnancy - (beta-human chorionic gonadotropin (HCG) to be performed if of child-bearing age)\n16. Liver failure (known severe liver disease or an alanine aminotransferase or an aspartate aminotransferase level that is 5 times the upper limit of normal)\n17. Kidney failure (estimated Glomerular Filtration Rate (eGFR =\\<30 mL/hr or receiving renal replacement therapy)\n18. Use of therapeutic anticoagulation or platelet antagonists\n19. Not for active treatment\n20. Unlikely to survive until the day after tomorrow'}, 'identificationModule': {'nctId': 'NCT05540834', 'acronym': 'VETtiPAT-ARF', 'briefTitle': 'Viscoelastic Testing Guided Tissue Plasminogen Activator Treatment in Acute Respiratory Failure', 'organization': {'class': 'OTHER', 'fullName': 'South West Sydney Local Health District'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'ICU001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'VET guided tPA administration + standard care', 'description': '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.', 'interventionNames': ['Drug: Alteplase']}, {'type': 'NO_INTERVENTION', 'label': 'Standard care', 'description': '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': [{'name': 'Alteplase', 'type': 'DRUG', 'otherNames': ['Tissue plasminogen activator', 'tPA', 'Actilyse', 'Activase'], 'description': 'The enzyme tissue plasminogen activator that cleaves plasminogen to form plasmin.', 'armGroupLabels': ['VET guided tPA administration + standard care']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1871', 'city': 'Liverpool', 'state': 'New South Wales', 'status': 'RECRUITING', 'country': 'Australia', 'contacts': [{'name': 'Anders Aneman, MD, PhD', 'role': 'CONTACT', 'email': 'anders.aneman@swsahs.nsw.gov.au', 'phone': '+61 2 8738 3400'}], 'facility': 'Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District', 'geoPoint': {'lat': -33.91938, 'lon': 150.92588}}], 'centralContacts': [{'name': 'Anders Aneman', 'role': 'CONTACT', 'email': 'Anders.Aneman@health.nsw.gov.au', 'phone': '+61 427915693'}, {'name': 'Lucy Coupland', 'role': 'CONTACT', 'email': 'l.coupland@unsw.edu.au', 'phone': '+61 419723330'}], 'overallOfficials': [{'name': 'Anders Aneman', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Sydney WAHS'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'South West Sydney Local Health District', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Anders Aneman', 'investigatorAffiliation': 'South West Sydney Local Health District'}}}}