COVID-19Phase 3NCT04400799
Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With COVID-19
A Phase 3 study testing Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml in people with COVID-19 and Pulmonary Embolism, Deep Vein Thrombosis, run by University of Zurich at 8 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- COVID-19, Pulmonary Embolism, Deep Vein Thrombosis
- What is being tested?
- Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 475 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 15 Jun 2020to 12 Apr 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment.
- Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C.
- 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
- Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant.
- 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.
- 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.
Who cannot join
- Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior VTE, acute confirmed symptomatic VTE, acute coronary syndrome.
- Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis:
- 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,
- previous VTE,
- histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable.
- 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.
Show all 14Show fewer
- Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial hemorrhage.
- Hemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days).
- Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy.
- Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days).
- Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity.
- Current use of dual antiplatelet therapy.
- Participation in other interventional studies over the past 30 days.
- Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Switzerland6 sites
University Hospital Basel
Basel, 4031
Clinic of Hematology, Oncology Institute of Southern Switzerland
Bellinzona
University Hospital Bern
Bern
Hôpitaux Universitaires Genève
Geneva
Clinica Luganese Moncucco
Lugano
University Hospital Zurich
Zurich, 8091
Germany2 sites
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Johannes Gutenberg-Universität Mainz
Mainz, 55122
About this study
Official title: Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With Coronavirus: The Multicenter Randomized Controlled Ovid Trial
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.
Read the detailed description
The following points represent, in summary, the rationale for studying the use of thromboprophylaxis in ambulatory patients with COVID-19:
- 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
- The cumulative risk of VTE in hospitalized COVID-19 patients is at least 20%, but possibly higher, as described in several publications
- The absolute VTE risk in COVID-19 patients requiring intensive care is 69% if screening strategies are implemented
- 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).
- Conditions
- COVID-19, Pulmonary Embolism, Deep Vein Thrombosis
- Being tested
- Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml
- Medical subject headings
- COVID-19, Pulmonary Embolism, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4MlDrug
daily incetion s.c. for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Test Group | Experimental | 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. Receives: Drug: Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml |
| Control Group | No intervention | No study drug |
What is being measured
The primary outcome is the main question the study is designed to answer.
hospitalizations
Measured: 30 days
all-cause death
Measured: 30 days
Secondary outcomes (5)
Number of cardiovascular events
including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke
Measured: within 14 days, 30 days, and 90 days of randomization
any hospitalizations
Measured: within 14 days, 30 days, and 90 days of randomization
all-cause death
Measured: within 14 days, 30 days, and 90 days of randomization
Net clinical benefit
measured by number of cardiovascular events, and major bleeding
Measured: within 14 days, 30 days, and 90 days of enrolment.
Disseminated intravascular coagulation
ISTH criteria, in-hospital diagnosis
Measured: within 14 days, 30 days, and 90 days of enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2020
- Study start15 Jun 2020
- Primary completion7 Feb 2022
- Study completion12 Apr 2022
Why it stopped: due to results from interim analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 475 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Insel Gruppe AG, University Hospital Bern, University Hospital, Geneva, Centre Hospitalier Universitaire Vaudois, University Hospital, Basel, Switzerland, Oncology Institute of Southern Switzerland, Clinica Luganese Moncucco, University Hospital Freiburg, Mainz University
- Responsible party
- Principal investigator, Nils Kucher, University of Zurich
- Investigators
- Nils Kucher, Prof., Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04400799
- Sponsor's protocol ID
- OVID Trial
- Status last verified
- May 2022
- First submitted
- 15 May 2020
- Last updated
- 25 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.
PubMed 37591523Barco S, Voci D, Held U, Sebastian T, Bingisser R, Colucci G, Duerschmied D, Frenk A, Gerber B, Gotschi A, Konstantinides SV, Mach F, Robert-Ebadi H, Rosemann T, Simon NR, Spechbach H, Spirk D, Stortecky S, Vaisnora L, Righini M, Kucher N; OVID investigators. Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet Haematol. 2022 Aug;9(8):e585-e593. doi: 10.1016/S2352-3026(22)00175-2. Epub 2022 Jun 30.
PubMed 35779558Barco S, Bingisser R, Colucci G, Frenk A, Gerber B, Held U, Mach F, Mazzolai L, Righini M, Rosemann T, Sebastian T, Spescha R, Stortecky S, Windecker S, Kucher N. Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Sep 9;21(1):770. doi: 10.1186/s13063-020-04678-4.
PubMed 32907635
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With Coronavirus: The Multicenter Randomized Controlled Ovid Trial
- ClinicalTrials.gov ID
- NCT04400799
- Acronym / sponsor ID
- OVID Trial
- Conditions
- COVID-19, Pulmonary Embolism, Deep Vein Thrombosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to results from interim analysis
- Enrolment
- 475 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Insel Gruppe AG, University Hospital Bern, University Hospital, Geneva, Centre Hospitalier Universitaire Vaudois, University Hospital, Basel, Switzerland, Oncology Institute of Southern Switzerland, Clinica Luganese Moncucco, University Hospital Freiburg, Mainz University
- Study start
- 15 Jun 2020 (actual)
- Primary completion
- 7 Feb 2022 (actual)
- Study completion
- 12 Apr 2022 (actual)
- First posted
- 26 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The following points represent, in summary, the rationale for studying the use of thromboprophylaxis in ambulatory patients with COVID-19:
- 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
- The cumulative risk of VTE in hospitalized COVID-19 patients is at least 20%, but possibly higher, as described in several publications
- The absolute VTE risk in COVID-19 patients requiring intensive care is 69% if screening strategies are implemented
- 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test Group | Experimental | Drug: Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4MlEnoxaparin (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. |
| Control Group | No intervention | –No study drug |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment.
- Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C.
- 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
- Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant.
- 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.
Key exclusion criteria (14 listed)
- Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior VTE, acute confirmed symptomatic VTE, acute coronary syndrome.
- Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis:
- 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.
- Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial hemorrhage.
- Hemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Mldaily incetion s.c. for 14 days | Drug | Test Group |
Primary outcome
hospitalizations
Time frame: 30 days
all-cause death
Time frame: 30 days
5 secondary outcomes
Number of cardiovascular events
Time frame: within 14 days, 30 days, and 90 days of randomization
any hospitalizations
Time frame: within 14 days, 30 days, and 90 days of randomization
all-cause death
Time frame: within 14 days, 30 days, and 90 days of randomization
Net clinical benefit
Time frame: within 14 days, 30 days, and 90 days of enrolment.
Disseminated intravascular coagulation
Time frame: within 14 days, 30 days, and 90 days of enrolment
Results and safety
The study was stopped early (reason given: due to results from interim analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2022.
- Derived from this study: PubMed 37591523Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.
- Derived from this study: PubMed 35779558Barco S, Voci D, Held U, Sebastian T, Bingisser R, Colucci G, Duerschmied D, Frenk A, Gerber B, Gotschi A, Konstantinides SV, Mach F, Robert-Ebadi H, Rosemann T, Simon NR, Spechbach H, Spirk D, Stortecky S, Vaisnora L, Righini M, Kucher N; OVID investigators. Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet Haematol. 2022 Aug;9(8):e585-e593. doi: 10.1016/S2352-3026(22)00175-2. Epub 2022 Jun 30.
- Derived from this study: PubMed 32907635Barco S, Bingisser R, Colucci G, Frenk A, Gerber B, Held U, Mach F, Mazzolai L, Righini M, Rosemann T, Sebastian T, Spescha R, Stortecky S, Windecker S, Kucher N. Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Sep 9;21(1):770. doi: 10.1186/s13063-020-04678-4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nils Kucher, Prof. principal investigator
University of Zurich
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml in people with COVID-19 and Pulmonary Embolism, Deep Vein Thrombosis, run by University of Zurich at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Switzerland, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: due to results from interim analysis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
hospitalizations (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04400799, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2022.