Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial

Davide Voci; Andrea Götschi; Ulrike Held; Roland Bingisser; Giuseppe Colucci; Daniel Duerschmied; Riccardo M Fumagalli; Bernhard Gerber; Barbara Hasse; Dagmar I Keller; Stavros V Konstantinides; François Mach; Silvana K Rampini; Marc Righini; Helia Robert-Ebadi; Thomas Rosemann; Stéphanie Roth-Zetzsche; Tim Sebastian; Noemi R Simon; David Spirk; Stefan Stortecky; Lukas Vaisnora; Nils Kucher; Stefano Barco; OVID investigators

doi:10.1016/j.thromres.2022.10.021

Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial

Thromb Res. 2023 Jan:221:157-163. doi: 10.1016/j.thromres.2022.10.021. Epub 2022 Nov 12.

Authors

Davide Voci¹, Andrea Götschi², Ulrike Held², Roland Bingisser³, Giuseppe Colucci⁴, Daniel Duerschmied⁵, Riccardo M Fumagalli¹, Bernhard Gerber⁶, Barbara Hasse⁷, Dagmar I Keller⁸, Stavros V Konstantinides⁹, François Mach¹⁰, Silvana K Rampini¹¹, Marc Righini¹², Helia Robert-Ebadi¹², Thomas Rosemann¹³, Stéphanie Roth-Zetzsche¹, Tim Sebastian¹, Noemi R Simon³, David Spirk¹⁴, Stefan Stortecky¹⁵, Lukas Vaisnora¹⁵, Nils Kucher¹⁶, Stefano Barco¹⁷; OVID investigators

Affiliations

¹ Department of Angiology, University Hospital Zurich, Zurich, Switzerland.
² Department of Biostatistics at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
³ Emergency Department, University Hospital Basel, Basel, Switzerland.
⁴ Service of Hematology, Clinica Luganese Moncucco, Lugano, Switzerland; University of Basel, Basel, Switzerland; Clinica Sant'Anna, Sorengo, Switzerland.
⁵ Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany; European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany; Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁶ Clinic of Hematology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; University of Zurich, Zurich, Switzerland.
⁷ University of Zurich, Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Switzerland.
⁸ University of Zurich, Zurich, Switzerland; Emergency Department, University Hospital Zurich, Zurich, Switzerland.
⁹ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Department of Cardiology, Democritus University of Thrace, Komotini, Greece.
¹⁰ Cardiology Division, Geneva University Hospital, Geneva, Switzerland.
¹¹ Division of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
¹² Division of Angiology and Hemostasis, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹³ Institute of Primary Care, University of Zurich, Zurich, Switzerland.
¹⁴ Institute of Pharmacology, University of Bern, Bern, Switzerland.
¹⁵ Department of Cardiology, Inselspital Bern, University of Bern, Bern, Switzerland.
¹⁶ Department of Angiology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland.
¹⁷ Department of Angiology, University Hospital Zurich, Zurich, Switzerland; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address: stefano.barco@usz.ch.

Abstract

Introduction: The benefits of early thromboprophylaxis in symptomatic COVID-19 outpatients remain unclear. We present the 90-day results from the randomised, open-label, parallel-group, investigator-initiated, multinational OVID phase III trial.

Methods: Outpatients aged 50 years or older with acute symptomatic COVID-19 were randomised to receive enoxaparin 40 mg for 14 days once daily vs. standard of care (no thromboprophylaxis). The primary outcome was the composite of untoward hospitalisation and all-cause death within 30 days from randomisation. Secondary outcomes included arterial and venous major cardiovascular events, as well as the primary outcome within 90 days from randomisation. The study was prematurely terminated based on statistical criteria after the predefined interim analysis of 30-day data, which has been previously published. In the present analysis, we present the final, 90-day data from OVID and we additionally investigate the impact of thromboprophylaxis on the resolution of symptoms.

Results: Of the 472 patients included in the intention-to-treat population, 234 were randomised to receive enoxaparin and 238 no thromboprophylaxis. The median age was 57 (Q1-Q3: 53-62) years and 217 (46 %) were women. The 90-day primary outcome occurred in 11 (4.7 %) patients of the enoxaparin arm and in 11 (4.6 %) controls (adjusted relative risk 1.00; 95 % CI: 0.44-2.25): 3 events per group occurred after day 30. The 90-day incidence of cardiovascular events was 0.9 % in the enoxaparin arm vs. 1.7 % in controls (relative risk 0.51; 95 % CI: 0.09-2.75). Individual symptoms improved progressively within 90 days with no difference between groups. At 90 days, 42 (17.9 %) patients in the enoxaparin arm and 40 (16.8 %) controls had persistent respiratory symptoms.

Conclusions: In adult community patients with COVID-19, early thromboprophylaxis with enoxaparin did not improve the course of COVID-19 neither in terms of hospitalisation and death nor considering COVID-19-related symptoms.

Keywords: Anticoagulation; COVID-19; Heparin; SARS-CoV2; Thrombosis; Venous thromboembolism.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Anticoagulants / therapeutic use
COVID-19*
Cardiovascular Diseases* / drug therapy
Enoxaparin / therapeutic use
Female
Humans
Male
Middle Aged
Outpatients
SARS-CoV-2
Treatment Outcome

Substances

Enoxaparin
Anticoagulants