Covid-19 Living Data

Trial NCT04401293
Publication Spyropoulos A, JAMA Intern Med (2021) (published paper)
Dates: 2020-05-08 to 2021-05-14
Funding: Public/non profit (Feinstein Institutes for Medical Research, the Broxmeyer Fellowship in Clinical Thrombosis, and grant R24AG064191 from the National Institute on Aging)
Conflict of interest: Yes

Methods
	RCT Blinding: single blinding
	Location : Multicenter / USA Follow-up duration (days): 30
Inclusion criteria	Hospitalized nonpregnant adults 18 years or older with COVID-19 diagnosed by nasal swab or serologic testing requirement for supplemental oxygen per investigator judgment and plasma D-dimer level greater than 4 times the upper limit of normal based on local laboratory criteria or a sepsis-induced coagulopathy score of 4 or greater
Exclusion criteria	Physician-determined need for full-dose anticoagulation or dual antiplatelet therapy bleeding within the past month active gastrointestinal or intracranial cancer bronchiectasis or pulmonary cavitation hepatic dysfunction with baseline international normalized ratio greater than 1.5 creatinine clearance (CrCl) less than 15 mL/min/1.73 m2 platelet count less than 25 000/μL a history of heparin-induced thrombocytopenia (HIT) within 100 days and hypersensitivity/intolerance to study drug or components
Interventions
	Treatment Therap AC 1 mg/kg subcutaneously twice daily if CrCl was 30 mL/min/1.73 m2 or greater or 0.5 mg/kg twice daily if CrCl was 15-29 mL/min/1.73 m2. Postdischarge anticoagulation allowed at the discretion of treating physicians.
	Control Intermediate dose Unfractionated heparin ≤ 22 500 IU subcutaneously daily; enoxaparin, 30 mg or 40 mg subcutaneously once or twice daily; dalteparin 2500 IU or 5000 IU subcutaneously daily. If CrCl fell below 15 mL/min/1.73 m2, enoxaparin was converted to treatment-dose intravenous UFH until CrCl >15 mL/min/1.73 m2. Postdischarge anticoagulation allowed at the discretion of treating physicians.
Participants
	Randomized participants : Therap AC=130 Intermediate dose=127
	Characteristics of participants N= 257 Mean age : NR 136 males Severity : Mild: n=* / Moderate: n=192 / Severe: n=39 Critical: n=13 Number of vaccinated participants: NR
Primary outcome
	In the register Composite outcome of arterial thromboembolic events, venous thromboembolic events and all-cause mortality at Day 30 ± 2 days. [ Time Frame: Day 30 ± 2 days ] Risk of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Day 30 ± 2 days.
	In the report VTE (symptomatic upper or lower extremity deep vein thrombosis, asymptomatic lower extremity proximal deep vein thrombosis, symptomatic pulmonary embolism, splanchnic vein thrombosis, or cerebral sinus thrombosis), or ATE (myocardial infarction, ischemic stroke, peripheral or systemic ATE) or death from any cause within 30 ± 2 days after randomization
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: N
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 full protocols with statistical analysis plan and supplementary appendices as well as data from contact with authors were used in data extraction and assessment of risk of bias. The primary and secondary outcomes in the article reflected those in the registry. The trial (n = 257) achieved its target sample size (n = 246). There is no change from the trial registration in the intervention and control treatments. The study was updated on the March 28th, 2022 with data from authors.