Optimal thromboprophylaxis and anticoagulant strategies in patients with COVID-19 pneumonia. The PROTHROMCOVID Trial

ABSTRACT

Introduction: Hospitalized patients with COVID-19 are at increased risk of venous and arterial thrombosis, ARDS, and death. The optimal dosage of thromboprophylaxis in patients is unknown. Objective: To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia.Design, Setting, and Participants: The PROTHROMCOVID multicenter randomized clinical trial enrolled noncritical hospitalized adult patients with COVID-19 pneumonia from February 1, 2021, to September 30, 2021, at 18 centers in Spain. Methods: Patients were randomized to prophylactic tinzaparin 4500IU or intermediate dose 100IU/kg or therapeutic tinzaparin 175IU/kg during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The patients were stratified at the time of randomization according to age, sex and the presence or absence of hypertension.The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non invasive mechanical ventilation or not, including high-flow nasal cannula oxygen, or death within 30 days. The main safety outcome was major bleeding at 30 days. Data were collected and adjudicated locally by non-blinded investigators through imaging, laboratory, and health record data. Results: Of 311 patients randomized, 300 were included in the analysis (mean [SD]age, 56.7 [14.6] years;men, 182 [60.7%];women, 118 [39.3%]). 106 patients (35.33%) were assigned to the prophylaxis group, 91 patients (30.33%) were allocated to the intermediate dose group and 103 patients (34.33%) were randomized to the anticoagulant dose group. The composite endpoint thrombotic event, need for invasive (IMV) or noninvasive mechanical ventilation (NIV) or HFT via nasal cannula or death at 30 days from randomization occurred in 58 patients (19.3%) of the whole population, 19 patients (17.09%) in prophylactic group, 20 (21.98%) in intermediate group and 19 (18.45%) in therapeutic group (P=0.72). No major bleeding were reported in the trial and non-major bleeding occurred in 5 patients (4.71%) in prophilactic, in 3 patients (3.2%) in intermediate arm and in 3 patients (2.9%) in therapeutic, without significant differences in each group (P=0.31). Conclusions: In non-critically ill patients with COVID 19, intermediate or full-dose of tinzaparin do not appear to offer benefit over standard prophylactic doses IU in the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death. Funding Acknowledgement Type of funding sources Private grant(s) and/or Sponsorship. Main funding source(s) Leo Pharma