Trial NCT04394377
Publication Lopes RD, Lancet , 2021 (published paper)
Dates: 2020-06-24 to 2021-02-26
Funding: Mixed (Coalition COVID-19 Brazil, Bayer SA.)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Brazil Follow-up duration (days): 60 | |
| Inclusion criteria | Hospitalised; ≥ 18 years old ; confirmation of COVID-19 based on specific tests used in clinical practice (RT-PCR, antigen test, or IgM test); symptoms for up to 14 days before randomization; elevated D-dimer concentration (above the upper limit of normal reference range per local laboratory). |
| Exclusion criteria | Indication for therapeutic anticoagulation during inclusion (e.g, diagnosis of VTE, AF, mechanical valve prosthesis); Platelets <50,000 /mm3; Use of ASA >100 mg; Use of P2Y12 inhibitor (clopidogrel, prasugrel, ticagrelor); Chronic use of NSAIDs; Sustained uncontrolled systolic BP ≥180 mm Hg or diastolic BP ≥100 mm Hg; INR >1·5; Patients contraindicated to therapeutic anticoagulation (active bleeding, liver failure, blood dyscrasia or prohibitive haemorrhage risk as evaluated by the investigator); Patients with DIC; History of haemorrhagic stroke or any intracranial bleeding at any time in the past or current intracranial neoplasm (benign or malignant), cerebral metastases, arteriovenous malformation, or aneurysm; Active cancer (excluding non-melanoma skin cancer) defined as cancer not in remission or requiring active chemotherapy or adjunctive therapies such as immunotherapy or radiotherapy; Hypersensitivity to rivaroxaban; Use of strong inhibitors of cytochrome P450 (CYP) 3A4 and/or P-gp (e.g., protease inhibitors, ketoconazole, itraconazole) and/or use of P-gp and strong CYP3A4 inducers (including, but not limited to, rifampin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, or St. John's Wort); Known HIV infection; Creatinine clearance <30 mL/min; Pregnancy or breastfeeding. |
| Interventions | |
| Treatment
Therapeutic anticoagulant Clinically stable patients: PO rivaroxaban, 20 mg once daily (15 mg once daily if reduced creatinine clearance). Clinically unstable patients: SC enoxaparin 1 mg/kg twice per day, or IV unfractionated heparin at a dose to achieve anti-Xa concentration or partial thromboplastin time targets. Unfractionated heparin preferred option for patients with renal dysfunction or disseminated intravascular coagulation. Treatment to day 30. |
|
| Control
Prophylactic anticoagulant ( / ) | |
| Participants | |
| Randomized 615 participants (n1=311 / n2= 304) | |
| Characteristics of participants N=615 Mean age : 56.6 368 males Severity : Mild: n=155 / Moderate: n=369/ Severe: n=53 Critical: n=38 | |
| Primary outcome | |
| In the register Hierarchical composite endpoint composed of mortality, number of days alive, number of days in the hospital and number of days with oxygen therapy at the end of 30 days. [ Time Frame: In 30 days ] | |
| In the report Hierarchical composite of time to death, duration of hospitalisation, or duration of supplemental oxygen use through 30 days; Major or clinically relevant non-major bleeding | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated
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| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the published article, the registry, published and unpublished protocols and statistical analysis plan, and supplementary appendices were used in data extraction and assessment of risk of bias. The WHO 8-point ordinal scale (on which data extracted were based) was not in the registry or first version of the study protocol, but was added in an approved amendment to the protocol within 2 weeks of start of recruitment. There were no differences between the protocol and the published article in populations, procedures or interventions.The study achieved its pre-specified target sample size. |