Ignite Creation Date:
2025-12-24 @ 10:44 PM
Ignite Modification Date:
2026-01-01 @ 7:47 PM
Study NCT ID:
NCT04408235
Status:
UNKNOWN
Last Update Posted:
2020-05-29
First Post:
2020-05-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D020141', 'term': 'Hemostatic Disorders'}, {'id': 'D000086382', 'term': 'COVID-19'}, {'id': 'D011014', 'term': 'Pneumonia'}], 'ancestors': [{'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D017984', 'term': 'Enoxaparin'}], 'ancestors': [{'id': 'D006495', 'term': 'Heparin, Low-Molecular-Weight'}, {'id': 'D006493', 'term': 'Heparin'}, {'id': 'D006025', 'term': 'Glycosaminoglycans'}, {'id': 'D011134', 'term': 'Polysaccharides'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['INVESTIGATOR'], 'maskingDescription': 'Randomisation will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (\\<75/≥75 years); 3) BMI (\\<30/≥30); 4) Co-morbidities (0-1/\\>2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This is a multicentre, randomised controlled, open label, investigator sponsored, two arms study.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 300}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2020-06', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-05', 'completionDateStruct': {'date': '2021-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-05-27', 'studyFirstSubmitDate': '2020-05-26', 'studyFirstSubmitQcDate': '2020-05-27', 'lastUpdatePostDateStruct': {'date': '2020-05-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-05-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:', 'timeFrame': 'through study completion, up to 30 days', 'description': '1. Death\n2. Acute Myocardial Infarction \\[AMI\\]\n3. Objectively confirmed, symptomatic arterial or venous thromboembolism \\[TE\\]\n4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation\n5. Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation'}], 'secondaryOutcomes': [{'measure': 'Any of the following events occurring within the hospital stay', 'timeFrame': 'through study completion, up to 30 days', 'description': '1. Death\n2. Acute Myocardial Infarction \\[AMI\\]\n3. Objectively confirmed, symptomatic arterial or venous thromboembolism \\[TE\\]\n4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation\n5. Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation\n6. Improvement of laboratory parameters of disease severity, including:\n\n * D-dimer level\n * Plasma fibrinogen levels\n * Mean Platelet Volume\n * Lymphocyte/Neutrophil ratio\n * IL-6 plasma levels'}, {'measure': 'Mortality at 30 days', 'timeFrame': '30 days', 'description': "Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation."}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['COVID-19', 'PNEUMONIA', 'COAGULOPATHY', 'LOW-MOLECULAR WEIGHT HEPARIN', 'ENOXAPARIN'], 'conditions': ['COVID', 'Pneumonia, Viral', 'Coagulation Disorder']}, 'referencesModule': {'references': [{'pmid': '32167524', 'type': 'BACKGROUND', 'citation': 'Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994.'}, {'pmid': '32347323', 'type': 'BACKGROUND', 'citation': 'Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020 Jun;46(6):1105-1108. doi: 10.1007/s00134-020-06059-6. Epub 2020 Apr 28. No abstract available.'}, {'pmid': '32220112', 'type': 'BACKGROUND', 'citation': 'Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 May;18(5):1094-1099. doi: 10.1111/jth.14817. Epub 2020 Apr 27.'}, {'pmid': '32073213', 'type': 'BACKGROUND', 'citation': 'Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.'}, {'pmid': '32281926', 'type': 'BACKGROUND', 'citation': 'Marietta M, Ageno W, Artoni A, De Candia E, Gresele P, Marchetti M, Marcucci R, Tripodi A. COVID-19 and haemostasis: a position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfus. 2020 May;18(3):167-169. doi: 10.2450/2020.0083-20. Epub 2020 Apr 8. No abstract available.'}, {'pmid': '32338827', 'type': 'BACKGROUND', 'citation': 'Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, Clark C, Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 May;18(5):1023-1026. doi: 10.1111/jth.14810. Epub 2020 Apr 27. No abstract available.'}, {'pmid': '32239799', 'type': 'BACKGROUND', 'citation': 'Thachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020 May;18(5):1020-1022. doi: 10.1111/jth.14821. Epub 2020 Apr 27. No abstract available.'}, {'pmid': '35244208', 'type': 'DERIVED', 'citation': 'Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.'}, {'pmid': '33502773', 'type': 'DERIVED', 'citation': 'Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.'}]}, 'descriptionModule': {'briefSummary': 'Randomized, controlled study conducted in hospitalized patients with severe COViD-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation.\n\nAim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000 IU once day) are:\n\n1. More effective to prevent clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first, during hospital stay:\n\n 1. Death\n 2. Acute Myocardial Infarction \\[AMI\\]\n 3. Objectively confirmed, symptomatic arterial or venous thromboembolism \\[TE\\]\n 4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients who are in standard oxygen therapy by delivery interfaces at randomisation\n 5. Need for invasive mechanical ventilation for patients who are in non-invasive mechanical ventilation at randomisation\n2. Similar in terms of major bleeding risk during hospital stay', 'detailedDescription': 'This is a multicentre, randomised controlled, open label, investigator sponsored, two arms study.\n\nThe study will involve 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Diseases Units, 1 Respiratory Diseases Unit.\n\nPatients who satisfy all inclusion criteria and do not have any exclusion criteria and have signed written informed consent, will be randomly assigned to a Low-Dose LMWH group (Control Group) or High-Dose LMWH group (Intervention Group) in a 1:1 ratio.\n\nControl Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 IU subcutaneously once day).\n\nIntervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table.\n\nThe study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group.\n\nThe treatments will be initiated as soon as possible after randomization (maximum allowed starting time 12h after randomization).\n\nPatients allocated to the two arms will maintain the doses of Enoxaparin, as stated in the protocol, until:\n\n1. hospital discharge or\n2. when at least one of the following events occurs:\n\n 1. Acute Myocardial Infarction \\[AMI\\]\n 2. Objectively confirmed, symptomatic arterial or venous thromboembolism \\[TE\\]\n 3. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation\n 4. Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation\n 5. Major bleeding\n 6. Any adverse events and clinical condition requiring interruption of the scheduled intervention according to the judgement of the physician in charge\n 7. Death\n\nThe decision about what type and dose of antithrombotic treatment to administer, after the interruption of assigned dose of Enoxaparin, will be left to clinical judgement of the physicians in charge.\n\nAny information about the type and dose of antithrombotic treatments administered after the interruption of the assigned dose of Enoxaparin will be collected until the hospital discharge or death.\n\nEach patient will be followed-up until hospital discharge. Information about the status (dead/alive) of patients who are discharged from hospital before 30 days will be sought on Day 30 from randomisation.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria (all required):\n\n* Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material)\n* Severe pneumonia defined by the presence of at least one of the following criteria:\n\n 1. Respiratory Rate ≥25 breaths /min\n 2. Arterial oxygen saturation≤93% at rest on ambient air\n 3. PaO2/FiO2 ≤300 mmHg\n* Coagulopathy, defined by the presence of at least one of the following criteria:\n\n 1. D-dimer \\>4 times the upper level of normal reference range\n 2. Sepsis-Induced Coagulopathy (SIC) score \\>4\n* No need for invasive mechanical ventilation\n\nExclusion Criteria:\n\n* Invasive mechanical ventilation\n* Thrombocytopenia (platelet count \\< 80.000 mm3)\n* Coagulopathy: INR \\>1.5, aPTT ratio \\> 1.4\n* Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation \\< 30 ml/min)\n* Known hypersensitivity to enoxaparin\n* History of heparin induced thrombocytopenia\n* Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations)\n* Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves).\n* Concomitant double antiplatelet therapy\n* Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed\n* Pregnancy or breastfeeding or positive pregnancy test\n* Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition)\n* Lack or withdrawal of informed consent'}, 'identificationModule': {'nctId': 'NCT04408235', 'acronym': 'COVID-19 HD', 'briefTitle': 'High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy', 'organization': {'class': 'OTHER', 'fullName': 'Azienda Ospedaliero-Universitaria di Modena'}, 'officialTitle': 'Randomised Controlled Trial Comparing High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy Not Requiring Invasive Mechanical Ventilation', 'orgStudyIdInfo': {'id': 'EudraCT N°: 2020-001972-13'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Low-Dose LMWH', 'description': 'Enoxaparin 4000 IU daily', 'interventionNames': ['Drug: Enoxaparin']}, {'type': 'EXPERIMENTAL', 'label': 'High-Dose LMWH', 'description': 'Enoxaparin 70 IU/kg twice daily', 'interventionNames': ['Drug: Enoxaparin']}], 'interventions': [{'name': 'Enoxaparin', 'type': 'DRUG', 'otherNames': ['Inhixa®'], 'description': 'Low-Dose LMWH: enoxaparin 4000 IU daily; High dose LMWH: 70 IU/kg twice daily', 'armGroupLabels': ['High-Dose LMWH', 'Low-Dose LMWH']}]}, 'contactsLocationsModule': {'locations': [{'zip': '41124', 'city': 'Modena', 'country': 'Italy', 'contacts': [{'name': 'Pasquale Mighali', 'role': 'CONTACT', 'email': 'mighali.pasquale@policlinico.mo.it', 'phone': '0594225868', 'phoneExt': '+39'}, {'name': 'Marco Marietta, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Azienda Ospedaliero-Universitaria', 'geoPoint': {'lat': 44.64783, 'lon': 10.92539}}], 'centralContacts': [{'name': 'Marco Marietta, MD', 'role': 'CONTACT', 'email': 'marco.marietta@unimore.it', 'phone': '0594224640', 'phoneExt': '+39'}, {'name': 'Pasquale Mighali', 'role': 'CONTACT', 'email': 'mighali.pasquale@aou.mo.it', 'phone': '0594225868', 'phoneExt': '+39'}], 'overallOfficials': [{'name': 'Marco Marietta, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Azienda Ospedaliero-Universitaria di Modena'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Azienda Ospedaliero-Universitaria di Modena', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Head, Hemostasis and Thrombosis Unit', 'investigatorFullName': 'Marco Marietta', 'investigatorAffiliation': 'Azienda Ospedaliero-Universitaria di Modena'}}}}