Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With COVID-19

The OVID study will show whether prophylactic-dose enoxaparin improves survival and reduces unplanned hospitalizations in ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation.

The following points represent, in summary, the rationale for studying the use of thromboprophylaxis in ambulatory patients with COVID-19: 1. The risk of thromboembolic events in patients with COVID-19 during anticoagulant prophylaxis exceeds that observed in medical patients, usually \<3%, even in the presence of seasonal viral infections 2. The cumulative risk of VTE in hospitalized COVID-19 patients is at least 20%, but possibly higher, as described in several publications 3. The absolute VTE risk in COVID-19 patients requiring intensive care is 69% if screening strategies are implemented 4. Half of the VTE events, mostly PE, were diagnosed at hospital admission, suggesting that these events developed during the quarantine period. Our hypothesis is that early thromboprophylaxis may prevent or limit coagulopathy, and reduce thromboembolic complications leading to hospitalization or death, in the presence of a mild COVID disease among outpatients. The study will be conducted as a multicentre randomized open-label controlled trial. In the study, a total of 1,000 adult patients aged 50 or older with COVID-19 and candidates to ambulatory treatment will be randomized to receive enoxaparin 40 mg sc qD or no treatment for a total of 14 days. The primary outcome will be assessed within 30 days of enrolment. We implemented two logistical solutions to integrate the process of SARS-CoV2 testing, pre-screening, screening (hot-line and flyers), in-hospital recruitment, enrolment and randomization/allocation. A nationwide OVID Hot-Line telephone number will be made available in 3 languages (German, French, Italian) for interested patients or test centers to contact the Hot-Line. Standard hygiene precautions will be met at the study centers to avoid spreading of SARS-CoV2 among other patients or health care workers. Principles of patient and investigator safety will be applied. Standard procedures concerning privacy, discussion with patients on details of the study, collection of informed consent, and instruction on how to administer the study medication will be maintained in conformity with GCP recommendations. This will also include outcome measurements to be conducted by telephone with standardized questionnaire. Enoxaparin (Clexane®) will be given at the recommended dose of 4,000 IU antiXa activity (40 mg/0.4 ml) once daily by SC injection for 14 days. A single interim analysis is planned at time when the outcomes of 50% of the patients (n=460 plus drop-outs) have been observed (anticipated in February 2022).