Ignite Creation Date:
2025-12-24 @ 7:02 PM
Ignite Modification Date:
2025-12-27 @ 2:24 PM
Study NCT ID:
NCT04757857
Status:
TERMINATED
Last Update Posted:
2023-01-25
First Post:
2021-02-08
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
COVID-19 Antithrombotic Rivaroxaban Evaluation
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000086382', 'term': 'COVID-19'}], 'ancestors': [{'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069552', 'term': 'Rivaroxaban'}], 'ancestors': [{'id': 'D013876', 'term': 'Thiophenes'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D009025', 'term': 'Morpholines'}, {'id': 'D010078', 'term': 'Oxazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Pragmatic, open-label, controlled randomized trial'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 660}}, 'statusModule': {'whyStopped': 'Sustained reduction in the number of new COVID-19 cases as well as lower than expected event rates', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2020-09-29', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-01', 'completionDateStruct': {'date': '2022-08-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-01-20', 'studyFirstSubmitDate': '2021-02-08', 'studyFirstSubmitQcDate': '2021-02-16', 'lastUpdatePostDateStruct': {'date': '2023-01-25', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-02-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-08-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Venous thromboembolic events (VTE)', 'timeFrame': 'Within 30 days from randomization', 'description': 'Defined as deep venous thrombosis, acute pulmonary embolism, other major venous thrombotic events.'}, {'measure': 'Mechanical ventilation free-survival', 'timeFrame': 'Within 30 days from randomization', 'description': 'Defined as survival without requirement of mechanical ventilation.'}, {'measure': 'Major Adverse Cardiovascular Events (MACE)', 'timeFrame': 'Within 30 days from randomization', 'description': 'Defined as acute myocardial infarction, stroke or acute limb ischemia'}, {'measure': 'Out-of-hospital death not attributed to major injury', 'timeFrame': 'Within 30 days from randomization', 'description': 'Death that occurred out of hospital due to any cause not related to trauma or other major injury'}], 'secondaryOutcomes': [{'measure': 'Time from randomization to hospitalization', 'timeFrame': '30 days from randomization', 'description': 'Defined as time elapsed since randomization to hospital admission'}, {'measure': 'Length of Hospitalization', 'timeFrame': '30 days from randomization', 'description': 'To assess the duration of hospitalization (length of hospital stay)'}, {'measure': 'Hospitalization in Intensive Care Unit', 'timeFrame': '30 days from randomization', 'description': 'Requirement of admission to ICU for intensive care'}, {'measure': 'Clinical requirement of mechanical ventilation', 'timeFrame': '30 days from randomization', 'description': 'Requirement of oxygen supplementation through invasive or non invasive mechanical ventilation.'}, {'measure': 'Clinical duration of mechanical ventilation', 'timeFrame': '30 days from randomization', 'description': 'Total time on oxygen supplementation through invasive or non invasive mechanical ventilation'}, {'measure': 'Composite vascular endpoint I', 'timeFrame': '30 days from randomization', 'description': 'Non-fatal myocardial infarction, non-fatal ischemic stroke or cardiovascular death, VTE'}, {'measure': 'Composite vascular endpoint II', 'timeFrame': '30 days from randomization', 'description': 'Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke or acute limb ischemia, VTE'}, {'measure': 'Major Bleeding', 'timeFrame': '30 days from randomization', 'description': 'Defined by International Society of Thrombosis and Hemostasis (ISTH) criteria'}, {'measure': 'Mortality', 'timeFrame': '30 days from randomization', 'description': 'Defined by all-cause deaths'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['SARS-Cov-2', 'COVID-19', 'Rivaroxaban', 'Antithrombotic'], 'conditions': ['COVID-19']}, 'referencesModule': {'references': [{'pmid': '37591523', 'type': 'DERIVED', 'citation': 'Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.'}, {'pmid': '37223666', 'type': 'DERIVED', 'citation': 'Avezum A, Oliveira Junior HA, Neves PDMM, Alves LBO, Cavalcanti AB, Rosa RG, Veiga VC, Azevedo LCP, Zimmermann SL, Silvestre OM, Seabra Prudente RC, Morales Kormann AP, Moreira FR, Boszczowski I, de Brito Sobrinho E, da Silva E Souza A, Seligman R, de Souza Paolino B, Razuk A, Diogenes de Magalhaes Feitosa A, Monteiro Belmonte PL, Freitas das Neves Goncalves P, Hernandes ME, Fagundes AL, Sarmet Esteves JM, Tognon AP, Eikelboom J, Berwanger O, Lopes RD, Oliveira GBF; Coalition VIII COVID-19 Brazil Investigators. Rivaroxaban to prevent major clinical outcomes in non-hospitalised patients with COVID-19: the CARE - COALITION VIII randomised clinical trial. EClinicalMedicine. 2023 Jun;60:102004. doi: 10.1016/j.eclinm.2023.102004. Epub 2023 May 18.'}, {'pmid': '37018790', 'type': 'DERIVED', 'citation': 'Oliveira GBF, Neves PDMM, Oliveira HA, Catarino DGM, Alves LBO, Cavalcanti AB, Rosa RG, Veiga VC, Azevedo LCP, Berwanger O, Lopes RD, Avezum A. Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE - Coalition COVID-19 Brazil VIII). Arq Bras Cardiol. 2023 Mar;120(3):e20220431. doi: 10.36660/abc.20220431. English, Portuguese.'}]}, 'descriptionModule': {'briefSummary': 'There are several ways in which the COVID-19 pandemic may affect the prevention and management of thrombotic and thromboembolic disease, either direct effect or the indirect effects of infection, such as through severe illness and hypoxia, may predispose patients to thrombotic events. The severe inflammatory response, critical illness, and underlying traditional risk factors may all predispose to thrombotic events. Therefore, considering the high-risk profile of cardiovascular comorbidities in patients with COVID-19, it is scientifically relevant to evaluate the use of anticoagulants as an adjunctive treatment in the context of COVID-19. Indeed, it will be tested the hypothesis that the use of moderate dose of rivaroxaban has a beneficial effect in the treatment of patients with a confirmed or probable diagnosis of COVID-19 infection, with no clear indication for hospitalization (mild and moderate cases) upon initial medical care, by reducing the need of hospitalization due to complications related to COVID-19.', 'detailedDescription': 'Initial studies suggest an inflammatory state and hypercoagulation in individuals with COVID-19. Apparently, the fact that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to Angiotensin Converting Enzyme 2 (ACE2) receptors can lead to ACE2 depletion by SARS-CoV-2 favoring the "harmful" ACE1 / angiotensin II and promoting tissue damage, including stroke. Recent observational studies indicate a higher rate of thromboembolism in patients with COVID-19, especially those in severe condition. They also report that, in patients treated with anticoagulants, complication rates were lower as compared with those not receiving anticoagulant therapies.\n\nMore recently, in a post-mortem study of patients with Covid-19 compared to recently published cases of influenza, the histopathological pattern on the periphery of the lungs of patients with Covid-19 revealed a diffuse alveolar lesion with infiltration of perivascular T cells and other vascular aspects, consisting of severe endothelial damage (endothelitis) associated with the presence of intracellular viruses and broken cell membranes. In addition, pulmonary vessels showed generalized thrombosis with microangiopathy, and alveolar capillary microthrombi were much more frequent in patients with COVID-19 than with severe influenza respiratory conditions.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Adults ≥ 18 years old;\n2. Evaluated in the emergency unit with probable or confirmed infection by COVID-19;\n3. Time between symptoms and inclusion ≤ 07 days \\*;\n4. Present mild or moderate signs and symptoms, with no clear indication for hospitalization;\n5. Present at least 2 risk factors for complication:\n\n * 65 years\n * Hypertension\n * Diabetes mellitus\n * Asthma\n * Chronic Obstructive Pulmonary Disease (COPD) or other chronic lung diseases\n * Smoking\n * Immunosuppression\n * Obesity (BMI\\> 30)\n * History of non-active cancer\n * Bed restriction or reduced mobility (≥50% of the wake time without walking)\n * Previous history of VTE\n * Use of oral hormonal contraceptives\n\nExclusion Criteria:\n\n1. Patients \\<18 years old;\n2. Hospitalization indication upon first medical care;\n3. Positive test for influenza in the first visit;\n4. Any known liver disease associated with coagulopathy; INR (International Normalized Ratio) \\> 1.5;\n5. Pregnant, lactating or with the possibility of becoming pregnant and without using an adequate contraceptive method;\n6. High risk of bleeding; History of bronchiectasis or pulmonary cavitation, Significant bleeding in the last 3 months, Active gastroduodenal ulcer, history of recent bleeding (within 3 months) or a high risk of bleeding;\n7. Stroke within 1 month or any history of hemorrhagic or lacunar stroke or any intracranial bleeding or any intracranial neoplasia, brain metastasis, arteriovenous malformation or brain aneurysm;\n8. Severe heart failure with left ventricular ejection fraction \\<30% (echocardiogram or other validated method previously documented) or symptoms of heart failure class III or IV of the New York Heart Association (NYHA);\n9. Estimated glomerular filtration rate (eGFR) \\<30 mL / min;\n10. Clinical indication for dual antiplatelet therapy or anticoagulation therapy (VTE, atrial fibrillation / flutter, mechanical valve prosthesis);\n11. Marked thrombocytopenia (platelets \\<50,000 / mm3);\n12. Non-cardiovascular disease that is associated with a poor prognosis, for example, active cancer (excluding non-melanoma skin cancer) defined as cancer without remission or requiring active chemotherapy or adjuvant therapies such as immunotherapy or radiation therapy or that increases the risk of an adverse reaction to the evaluated interventions;\n13. History of hypersensitivity or known contraindication to rivaroxaban;\n14. Systemic treatment with strong inhibitors of Cytochrome P450 3A4 (CYP3A4) and glycoprotein p (Pgp) (for example, systemic azole antimycotics, such as ketoconazole and human immunodeficiency virus \\[HIV\\] protein inhibitors, such as ritonavir) or strong inducers of CYP 3A4, that is, rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine;\n15. Current treatment being tested;\n16. Concomitant participation in another study with experimental drugs in the context of COVID;\n17. Use of chloroquine or hydroxychloroquine associated with azithromycin;\n18. Active cancer;\n19. Other contraindications to rivaroxaban;'}, 'identificationModule': {'nctId': 'NCT04757857', 'acronym': 'CARE', 'briefTitle': 'COVID-19 Antithrombotic Rivaroxaban Evaluation', 'organization': {'class': 'OTHER', 'fullName': 'Hospital Alemão Oswaldo Cruz'}, 'officialTitle': 'Randomized, Pragmatic, Open Controlled Multicentre Study, Evaluating the Use of Rivaroxaban in Mild or Moderate COVID-19 Patients', 'orgStudyIdInfo': {'id': '36066320.5.1001.0070'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Rivaroxaban 10 mg', 'description': 'Participants will receive, from the 1st to the 14th day, a dose of 10 mg of rivaroxaban - OA (Oral Administration).', 'interventionNames': ['Drug: Rivaroxaban 10 mg']}, {'type': 'NO_INTERVENTION', 'label': 'Best locally standardized care', 'description': 'According to the study protocol, participating investigators are advised to follow the best available local practice in each participating site. There is no formal recommendation for any particular COVID-19 treatment, except symptomatic therapies.'}], 'interventions': [{'name': 'Rivaroxaban 10 mg', 'type': 'DRUG', 'otherNames': ['Xarelto'], 'description': 'Rivaroxaban pharmaceutical form will be tablets of 10 mg', 'armGroupLabels': ['Rivaroxaban 10 mg']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Barbalha', 'state': 'Ceará', 'country': 'Brazil', 'facility': 'Hospital Maternidade São Vicente de Paulo', 'geoPoint': {'lat': -7.31111, 'lon': -39.30417}}, {'city': 'Feira de Santana', 'state': 'Estado de Bahia', 'country': 'Brazil', 'facility': 'Clínica Senhor do Bonfim', 'geoPoint': {'lat': -12.26667, 'lon': -38.96667}}, {'city': 'Brasília', 'state': 'Federal District', 'country': 'Brazil', 'facility': 'Hospital de Base do Distrito Federal', 'geoPoint': {'lat': -15.77972, 'lon': -47.92972}}, {'city': 'Goiânia', 'state': 'Goiás', 'country': 'Brazil', 'facility': 'Hospital de Campanha Covid-19 Goiânia/Sesgo', 'geoPoint': {'lat': -16.67861, 'lon': -49.25389}}, {'city': 'Trindade', 'state': 'Goiás', 'country': 'Brazil', 'facility': 'Hospital Estadual de Urgências de Trindade/SESGO', 'geoPoint': {'lat': -16.64944, 'lon': -49.48889}}, {'zip': '30190-130', 'city': 'Belo Horizonte', 'state': 'Minas Gerais', 'country': 'Brazil', 'facility': 'Núcleo de Pesquisa Clínica do Hospital Vera Cruz', 'geoPoint': {'lat': -19.92083, 'lon': -43.93778}}, {'city': 'Belo Horizonte', 'state': 'Minas Gerais', 'country': 'Brazil', 'facility': 'Hospital São Lucas', 'geoPoint': {'lat': -19.92083, 'lon': -43.93778}}, {'city': 'Passos', 'state': 'Minas Gerais', 'country': 'Brazil', 'facility': 'Santa Casa de Misericórdia de Passos', 'geoPoint': {'lat': -20.71889, 'lon': -46.60972}}, {'city': 'Maringá', 'state': 'Paraná', 'country': 'Brazil', 'facility': 'Hospital Universitário Regional de Maringá', 'geoPoint': {'lat': -23.42528, 'lon': -51.93861}}, {'zip': '66060-575', 'city': 'Belém', 'state': 'Pará', 'country': 'Brazil', 'facility': 'Beneficencia Nipo Brasileira Da Amazonia', 'geoPoint': {'lat': -1.45583, 'lon': -48.50444}}, {'zip': '66093-904', 'city': 'Belém', 'state': 'Pará', 'country': 'Brazil', 'facility': 'Hospital Adventista de Belém', 'geoPoint': {'lat': -1.45583, 'lon': -48.50444}}, {'city': 'Bento Gonçalves', 'state': 'Rio Grande do Sul', 'country': 'Brazil', 'facility': 'Associação Dr. Bartholomeu Tacchini', 'geoPoint': {'lat': -29.17139, 'lon': -51.51917}}, {'zip': '99010-080', 'city': 'Passo Fundo', 'state': 'Rio Grande do Sul', 'country': 'Brazil', 'facility': 'Hospital São Vicente de Paulo', 'geoPoint': {'lat': -28.26278, 'lon': -52.40667}}, {'city': 'Porto Alegre', 'state': 'Rio Grande do Sul', 'country': 'Brazil', 'facility': 'Hospital das Clínicas de Porto Alegre', 'geoPoint': {'lat': -30.03283, 'lon': -51.23019}}, {'zip': '97900015', 'city': 'Santa Maria', 'state': 'Rio Grande do Sul', 'country': 'Brazil', 'facility': 'Hospital Universitario de Santa Maria', 'geoPoint': {'lat': -29.68417, 'lon': -53.80694}}, {'city': 'Blumenau', 'state': 'Santa Catarina', 'country': 'Brazil', 'facility': 'Clínica Procárdio Ltda', 'geoPoint': {'lat': -26.91944, 'lon': -49.06611}}, {'zip': '89204-250', 'city': 'Joinville', 'state': 'Santa Catarina', 'country': 'Brazil', 'facility': 'H&W Cardiologia LTDA', 'geoPoint': {'lat': -26.30444, 'lon': -48.84556}}, {'zip': '13600-655', 'city': 'Araras', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Irmandade santa Casa de Araras', 'geoPoint': {'lat': -22.35694, 'lon': -47.38417}}, {'city': 'Barueri', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Alphacor Cardiologia Clínica e Diagnóstica LTDA', 'geoPoint': {'lat': -23.51056, 'lon': -46.87611}}, {'city': 'Blumenau', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Maestri e Kormann Consultoria Medico-Cientifica LTDA - EPP'}, {'city': 'Caraguatatuba', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Regional do Litoral Norte - Instituto Sócrates Guanaes', 'geoPoint': {'lat': -23.62028, 'lon': -45.41306}}, {'city': 'Caraguatatuba', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Santos Dumont Litoral Norte', 'geoPoint': {'lat': -23.62028, 'lon': -45.41306}}, {'city': 'Cordeirópolis', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital de Corderiopolis', 'geoPoint': {'lat': -22.48194, 'lon': -47.45667}}, {'city': 'Itanhaém', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Regional Jorge Rossman - Instituto Sócrates Guanaes', 'geoPoint': {'lat': -24.18306, 'lon': -46.78889}}, {'city': 'Matão', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Carlos Fernando Malzoni', 'geoPoint': {'lat': -21.60333, 'lon': -48.36583}}, {'zip': '90035-001', 'city': 'Porto Alegre', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Moinhos de Vento'}, {'city': 'Registro', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Regional de Registro - Instituto Sócrates Guanaes', 'geoPoint': {'lat': -24.4875, 'lon': -47.84361}}, {'city': 'Ribeirão Preto', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Unimed Ribeirão Preto', 'geoPoint': {'lat': -21.1775, 'lon': -47.81028}}, {'zip': '15015-110', 'city': 'São José do Rio Preto', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Kaiser Clinica e Hospital Dia', 'geoPoint': {'lat': -20.81972, 'lon': -49.37944}}, {'city': 'São José do Rio Preto', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Braile Hospital Dia Ltda', 'geoPoint': {'lat': -20.81972, 'lon': -49.37944}}, {'zip': '12 243 000', 'city': 'São José dos Campos', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Policlin', 'geoPoint': {'lat': -23.17944, 'lon': -45.88694}}, {'city': 'São José dos Campos', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Regional de São José dos Campos - Instituto Sócrates Guanaes', 'geoPoint': {'lat': -23.17944, 'lon': -45.88694}}, {'city': 'Votuporanga', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Santa Casa de Misericórdia de Votuporanga', 'geoPoint': {'lat': -20.42278, 'lon': -49.97278}}, {'zip': '01323-903', 'city': 'São Paulo', 'country': 'Brazil', 'facility': 'International Research Center - Hospital Alemão Oswaldo Cruz', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}, {'zip': '01506-000', 'city': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Leforte Liberdade', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}, {'zip': '05403-010', 'city': 'São Paulo', 'country': 'Brazil', 'facility': 'Incor - Instituto do Coração do Hospital das Clínicas da FMUSP', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}], 'overallOfficials': [{'name': 'Álvaro Avezum, Ph.D', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'International Research Center - Hospital Alemão Oswaldo Cruz'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hospital Alemão Oswaldo Cruz', 'class': 'OTHER'}, 'collaborators': [{'name': 'Bayer', 'class': 'INDUSTRY'}, {'name': 'Hospital Israelita Albert Einstein', 'class': 'OTHER'}, {'name': 'Hospital do Coracao', 'class': 'OTHER'}, {'name': 'Hospital Sirio-Libanes', 'class': 'OTHER'}, {'name': 'Hospital Moinhos de Vento', 'class': 'OTHER'}, {'name': 'Brazilian Research In Intensive Care Network', 'class': 'NETWORK'}, {'name': 'Brazilian Clinical Research Institute', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Research Manager - International Research Center', 'investigatorFullName': 'Álvaro Avezum Junior', 'investigatorAffiliation': 'Hospital Alemão Oswaldo Cruz'}}}}