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).
Drug: Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml
daily incetion s.c. for 14 days
Inclusion Criteria:
1. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days
and eligible for ambulatory treatment.
2. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or
body temperature >37.5° C.
3. Ability of the patient to travel to the study center by private transportation,
performed either by accompanying person from same household or by the patient
him/herself
4. Ability to comply with standard hygiene requirements at the time of in-hospital visit,
including a face mask and hand disinfectant.
5. Ability to walk from car to study center or reach it using a wheel chair transport
with the help of an accompanying person from the same household also complying with
standard hygiene requirements.
6. Ability to self-administer prefilled enoxaparin injections after instructions received
at the study center or availability of a person living with the patient to administer
enoxaparin.
Exclusion Criteria:
1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g.
atrial fibrillation, prior VTE, acute confirmed symptomatic VTE, acute coronary
syndrome.
2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history,
comorbidity or predisposing strong risk factors for thrombosis:
1. Any of the following events occurring in the prior 30 days: fracture of lower
limb, hospitalization for heart failure, hip/knee replacement, major trauma,
spinal cord injury, stroke,
2. previous VTE,
3. histologically confirmed malignancy, which was diagnosed or treated (surgery,
chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or
inoperable.
3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization,
transfusion, surgical intervention, invasive procedures, occurring in a critical
anatomical site, or causing disability) within 30 days prior to randomization or sign
of acute bleeding.
4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute
intracranial hemorrhage.
5. Hemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory
test (<90 days).
6. Subjects with any known coagulopathy or bleeding diathesis, including known
significant liver disease associated with coagulopathy.
7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using
the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days).
8. Contraindications to enoxaparin therapy, including prior heparin-induced
thrombocytopenia and known hypersensitivity.
9. Current use of dual antiplatelet therapy.
10. Participation in other interventional studies over the past 30 days.
11. Non-compliance or inability to adhere to treatment or lack of a family environment or
support system for home treatment.
Universitätsklinikum Freiburg
Freiburg, Germany
Johannes Gutenberg-Universität Mainz
Mainz, Germany
University Hospital Basel
Basel, Switzerland
Clinic of Hematology, Oncology Institute of Southern Switzerland
Bellinzona, Switzerland
University Hospital Bern
Bern, Switzerland
Hôpitaux Universitaires Genève
Geneva, Switzerland
Clinica Luganese Moncucco
Lugano, Switzerland
University Hospital Zurich
Zürich, Switzerland
Nils Kucher, Prof., Principal Investigator
University of Zurich