NCT04600141.

Study name	Clinical efficacy of heparin and tocilizumab in patients with severe COVID‐19 infection: a randomized clinical trial
Starting date	10 November  2020
Contact information	Ludhmila A Hajjar, MD, PhD Fundação São Francisco Xavier Ipatinga, Minas Gerais, Brazil 551126614177 | ludhmila@terra.com.br
Methods	Open‐label, parallel‐assignment RCT
Participants	308 participants, ≥ 18 years, female and male Inclusion criteria: Age ≥ 18 years Informed consent form signed by the patient or guardian or by audio with the guardian Positive result for COVID‐19 in PCR in nasopharyngeal swab or tracheal secretion up to 10 days before the inclusion and radiological evidence of COVID‐19, by chest radiography or chest CT Need for ≥ 4 L of supplemental oxygen to maintain peripheral oxygen saturation ≥ 93% or need for invasive mechanical ventilation Exclusion criteria: Risk of bleeding: clinical: active bleeding, major surgery in the last 30 days, GI bleeding within 30 days laboratory: platelet count < 50,000, INR > 2 or aPTT > 50 s Known or suspected adverse reaction to UFH, including HIT Adverse reaction or allergy to tocilizumab Use of any of the following treatments: UFH to treat a thrombotic event within 12 h before inclusion; LMWH in therapeutic dose within 12 h before inclusion; warfarin (if used 7 days before and if INR > 2; thrombolytic therapy within 3 days before; and use of glycoprotein IIb/IIIa inhibitors within the previous 7 days Pregnant or lactating Absolute indication of anticoagulation due to atrial fibrillation or diagnosed thromboembolic event Refusal by family members and/or patient Active TB Bacterial infection confirmed by culture Neutropenia (< 1000 neutrophils/mm³) Use of another immunosuppressive therapy that is not a corticosteroid Septic shock
Interventions	Experimental: Group 1 ‐ therapeutic anticoagulation with tocilizumab IV UFH initiated at a dose of 18 IU/kg/h, adjusted according to a nomogram to achieve a aPTT of 1.5 to 2.0 times the reference value associated with 8 mg/kg/tocilizumab infusion/IV dose in a single dose, or SC LMWH ‐ enoxaparin 1 mg/kg per dose every 12 h associated with an infusion of tocilizumab 8 mg/kg/dose in a single dose Group 2 ‐ prophylactic anticoagulation with tocilizumab SC UFH 5000 IU every 8 h associated with an infusion of tocilizumab 8 mg/kg/IV dose in a single dose; or SC LMWH ‐ enoxaparin 40 mg daily associated with an infusion of tocilizumab 8 mg/kg/IV dose in a single dose Comparator: Group 1 ‐ therapeutic anticoagulation IV UFH started at a dose of 18 IU/kg/h, adjusted according to a nomogram to achieve an aPTT of 1.5‐2.0 times the reference value; or SC LMWH ‐ enoxaparin 1 mg/kg per dose every 12 h Group 2 ‐ prophylactic anticoagulation SC UFH 5000 IU every 8 h; or SC LMWH ‐ enoxaparin 40 mg daily
Outcomes	Primary Proportion of patients with clinical improvement (time frame: 30 days) Not hospitalised, with no limitations on activities Not hospitalised, but limited to activities Hospitalised, with no need for supplemental oxygen Hospitalised, needing supplemental oxygen Hospitalised, requiring high‐flow oxygen therapy, non‐invasive mechanical ventilation or both Hospitalised, requiring ECMO, invasive mechanical ventilation or both Death Secondary Hospital and ICU length of stay (time frame: 30 days) Duration of invasive mechanical ventilation (time frame: 30 days) Duration of vasopressor use (time frame: 30 days) Renal failure by AKIN criteria (time frame: 30 days) Incidence of cardiovascular complications (time frame: 30 days) Incidence of VTE (time frame: 30 days) Mortality (time frame: 30, 60 and 90 days)
Notes	NCT04600141 | No data provided