Ramacciotti 2022.

Study characteristics
Methods	Prospective, open‐label, multicentre RCT
Participants	Number of participants: 320 Age: between 18 and 90 years old Gender: male (191 participants) and female (127 participants) Inclusion criteria Male and non‐pregnant female patients 18 years of age or older Positive RT‐PCR assay for SARS‐CoV‐2 in a respiratory tract sample Pneumonia confirmed by chest imaging Additional risk factors for VTE, as indicated by a total modified IMPROVE risk score of 4 or higher Have received thromboprophylaxis with LMWH, fondaparinux, or UFH during the index hospitalisation Exclusion criteria Age < 18 years Refusal of informed consent Physician decision that involvement in the trial was not in the patient's best interest Patients with a medical indication for anticoagulation therapy at the time of inclusion (e.g. diagnosis of VTE, atrial fibrillation, mechanical valve prosthesis) Platelets < 50,000/mm3 Patients with contraindications to anticoagulation (active bleeding, liver failure, blood dyscrasia, or prohibitive haemorrhagic risk in the investigator's assessment) 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 Use of strong inhibitors of CYP3A4 and/or P‐gp (e.g. protease inhibitors, ketoconazole, itraconazole) and/or use of P‐gp and strong inducers of CYP3A4 (e.g. rifampicin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, or St. John's wort) Creatinine clearance < 30 mL/min Pregnancy or breastfeeding Known HIV infection Presence of 1 of the following uncontrolled or unstable cardiovascular diseases: stroke, ECG‐confirmed acute ischaemia or myocardial infarction, and/or clinically significant dysrhythmia
Interventions	Intervention: rivaroxaban 10 mg once daily for 35 days post‐hospital discharge Control: no intervention
Outcomes	Planned and reported Primary outcomes: VTE and VTE‐related death (time frame: at day 35 post‐hospital discharge) Secondary outcomes: Major bleeding (time frame: at day 35 post‐hospital discharge) Other outcomes: A composite of myocardial infarction, stroke, arrhythmias, heart failure, VTE, and all‐cause death (time frame: at day 35 post‐hospital discharge) Days alive out of the hospital at 35 days (time frame: at day 35 post‐hospital discharge D‐dimer (time frame: at day 35 post‐hospital discharge) C‐reactive protein (time frame: at day 35 post‐hospital discharge)
Funding	Bayer
Declaration of interest	ER reports grants and consulting fees from Bayer and Pfizer; grants from the Brazilian Ministry of Science and Technology; and personal fees from Aspen Pharma, Biomm Pharma, and Daiichi‐Sankyo, outside of the submitted work. LBA reports grants from Bayer, Pfizer, and the Brazilian Ministry of Science and Technology. DC reports personal fees from Bayer, Janssen, Daiichi‐Sankyo, and Pfizer; and grants from Stago. ACS reports consulting fees from Janssen Research & Development, Bayer, Portola, Boehringer Ingelheim, Bristol Myers Squibb, and ATLAS group; and grants from Janssen and Boehringer Ingelheim. MLS reports personal fees from Bayer, Pfizer, and Sanofi. EEJ reports consulting and personal fees form Bayer. CD reports consulting and personal fees from Bayer, Novartis, and Daiichi‐Sankyo. SMVS reports personal fees from Bayer. RCC reports personal fees from Boehringer Ingelheim and AstraZeneca. ATaf reports personal fees from Janssen and Recovery Force and grants from Bio Tap, Idorsia, Bristol Myers Squibb, Novo Nordisk, Janssen, and Doasense. RDL reports grants and personal fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and personal fees from Amgen, Bayer, and Boehringer Ingelheim, outside of the submitted work. All other authors declare no competing interests.
Notes	Quote: "The study funder had no role in the planning and design of the study, data collection, analysis, and interpretation, nor writing of the manuscript."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: 'Randomisation was done in permuted blocks of variable size, using a central, concealed, web‐based, automated randomisation system (RedCap, version 11.0.3).' Comment: information from the study article.
Allocation concealment (selection bias)	Low risk	Quote: 'Patients were randomly allocated in a 1:1 ratio to receive either thromboprophylaxis with rivaroxaban 10 mg/day or regular follow‐up (no anticoagulation) for 35 days.' Quote: 'Randomisation was done in permuted blocks of variable size, using a central, concealed, web‐based, automated randomisation system (RedCap, version 11.0.3).' Comment: information from the study article.
Blinding of participants and personnel (performance bias)	High risk	Quote: 'The MICHELLE trial was an open‐label study, with no masking of investigators or patients to group allocation.' Comment: information from the study article.
Blinding of outcome assessment (detection bias)	Low risk	Quote: 'An independent clinical events classification committee, whose members were unaware of the study treatment assignment, adjudicated all venous and arterial thromboembolic and bleeding events, and causes of death. ' Comment: information from the study article.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote 'From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n = 160 (50%)) or no anticoagulation (n = 160 (50%). Thus, 159 patients per group were included in the intention‐to‐treat analysis.'
Selective reporting (reporting bias)	Low risk	The study protocol is available and all of the study's prespecified (primary and secondary) outcomes that are of interest in the review have been reported in the prespecified way.
Other bias	Low risk	We did not find other bias in the study.

AE: adverse events
BMI: body mass index
CD4: cluster of differentiation 4
COPD: chronic obstructive pulmonary disease
COVID‐19: coronavirus disease 2019
CYP3A: cytochrome P450 3A
DOAC: direct oral anticoagulant
DM: diabetes mellitus
DVT: deep vein thrombosis
ECG: electrocardiogram
eGFR: estimated glomerular filtration rate
GI: gastrointestinal
GFR: glomerular filtration rate
ICU: intensive care unit
IMPROVE: International Medical Prevention Registry on Venous Thromboembolism 
ISTH: International Society on Thrombosis and Haemostasis
LMWH: low‐molecular‐weight heparin
NHLBI: National Heart, Lung, and Blood Institute
NIH: National Institutes of Health
PAD: peripheral artery disease
PCI: percutaneous coronary intervention
PE: pulmonary embolism
P‐gp: permeability glycoprotein
RCT: randomised controlled trial
RT‐PCR: reverse transcription polymerase chain reaction 
SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2
sc: subcutaneously
TRI: Translational Research Institute
UFH: unfractionated heparin
VKA: vitamin K antagonist
VTE: venous thromboembolism