Covid-19 Living Data

Trial NCT04604327
Publication Marcos M, Thromb Haemost (2021) (published paper)
Dates: 2020-10-26 to 2021-05-30
Funding: Mixed (This trial was an investigator-initiated study. Laboratorios Farmacéuticos ROVI kindly provided the study drugs, but did not participate in any other step of the clinical trial process.)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Spain Follow-up duration (days): 30
Inclusion criteria	Age 18 or older Hospitalization at the conventional ward due to mild or moderate (CURB65 90%) COVID-19 pneumonia. Maximum allowed time between hospitalization and randomization is 48 hours 3-4 points according to the WHO ordinal scale Confirmed COVID-19 diagnosis by PCR or other validated test Baseline D-Dimer >500 ng/mL Signed informed consent The patient, according to investigator’s opinion, is able to deal with all the requirements of the clinical trial
Exclusion criteria	Need of intensive care unit admission Moderate or severe adult respiratory distress syndrome Body weight <50Kg Creatinine clearance (Cockroft-Gault) <30ml/min Severe liver disease (elevation of hepatic enzymes 3 times above the upper limit of normal) Thrombocytopenia <75,000/mm3 History of coagulopathy or thrombocytopathy Active bleeding of increased bleeding risk due to impairment of haemostasis Recent (1 month) central nervous system o gastrointestinal bleeding Lesions of surgery involving central nervous system, eyes or inner ear in the last 2 months Presence of organic lesions with high bleeding risk (e.g. active peptic ulcer, hemorragic, stroke, brain aneurism or tumor) Planned surgery or interventional procedure requiring regional anesthesia Uncontrolled arterial hypertension Acute or subacute bacterial endocarditis Need of therapeutic anticoagulation for other reasons (e.g. atrial fibrillation, valvular prosthesis, venous thromboembolism) Need of antiplatelet therapy Simultaneous participation in another clinical trial (use of drugs against COVID-19 in the setting of local clinical management protocols is allowed) Previous history of heparin-induced thrombocytopenia Hypersensitivity or allergy to sodic bemiparin, heparin, compounds of porcine origin or any of the excipients
Interventions
	Treatment Therap AC 115 IU/Kg subcutaneously, adjusted to body weight (7,500 IU for patients between 50-70 Kg; 10,000 IU for patients weighing >70-100 Kg; 12,500 IU for patients who weighed >100 Kg) once a day for 10 days (extended at the discretion of the treating physician)
	Control Prophylactic AC 3,500 IU subcutaneously once a day for 10 days (extended at the discretion of the treating physician)
Participants
	Randomized NR Analyzed 65 participants Prophylactic AC=33 Therap AC=32
	Characteristics of participants N= 65 Mean age : NR 41 males Severity : Mild: n=27 / Moderate: n=38 / Severe: n=0 Critical: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Clinical deterioration [ Time Frame: 10 days ] Combined outcome that includes number of patients who suffer any of the following: Death, ICU admission, mechanical ventilatory support, progression to moderate or severe ARDS (according to Berlin criteria) or arterial or venous thrombosis.
	In the report Composite of death, ICU admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress syndrome and venous or arterial thrombosis within 10 days of enrollment
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
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	High
General comment	In addition to the published article, the study registry was used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan was available. There is no change from the trial registration in the intervention and control treatments. he primary outcome in the article reflects the primary outcome in the registry. The secondary outcomes in the article were not included in the registry. Recruitment to the study was terminated after an interim analysis, conducted at 40% of target sample size, because of both slow recruitment and futility. As a result the trial did not achieve its target sample size (164 versus 65).