A Joint Analysis of Two Randomized Controlled Trials on Enoxaparin for Covid-19

ABSTRACT

Background: COVID-19 carries a high risk of vascular thrombosis. This joint analysis of two randomized-controlled trials (RCTs) aims to assess the safety and efficacy of enoxaparin at therapeutic dose compared to prophylactic dose in people hospitalized with COVID-19. Method(s) A joint analysis of two RCTs, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), was performed. Both studies enrolled inpatients with COVID-19- associated respiratory compromise (as identified by respiratory rate >=25 breaths/min or arterial oxygen saturation <=93% at rest or PaO2/FiO2 <=300 mmHg for COVID-19 HD and by PaO2/FiO2 <=250 mmHg for EMOS-COVID) and/or coagulopathy (D-dimer > 2000 ng/ml for both RCTs or sepsis-Induced coagulopathy score >4 for COVIDHD). In both RCTs patients were randomly assigned to two arms enoxaparin at prophylactic dose (standard 4.000 IU;in the EMOS-COVID 6000 IU if body weight >100 kg) and at therapeutic dose (70 U/Kg every 12 h). The primary efficacy endpoint of the joint analysis was clinical worsening, defined as the occurrence of at least one among in-hospital death;acute myocardial infarction;symptomatic arterial or venous thromboembolism;need of either Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) in patients who were in standard oxygen therapy at randomization;need for IMV in any patient. The primary outcome was assessed as time-to-event, described with hazard ratio (HR) and with Kaplan-Meier survival estimate. The primary safety endpoint was major bleeding for both trials and for the joint analysis. Result(s) COVID-19 HD enrolled 142 people between July 2, 2020 and February 15, 2022, while EMOS-COVID enrolled 141 people from July 27, 2020 to June 5, 2021, resulting in 283 patients included in this joint analysis. Two-hundredseven (73.1%) were males, with a mean age of 61.1 years (SD +/-10.7), a mean BMI of 29.7 kg/m2 (SD +/-5.0), and 115 (40.6%) were on NIV or Cpap at randomization, with no significant difference between the study groups. 21/139 people in the high dose group reached the primary endpoint compared to 32/144 in the prophylactic group (HR 0.63, 95%CI 0.36 to 1.10). Figure 1 shows the Kaplan- Meier survival estimates of clinical worsening. No major bleeding was observed during the study time. Conclusion(s) The results of this joint analysis did not highlight significant differences in clinical worsening between COVID-19 patients that received enoxaparin at therapeutic compared to prophylactic dose. (Figure Presented).