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Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With COVID-19

Primary Purpose

COVID-19, Pulmonary Embolism, Deep Vein Thrombosis

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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:
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.
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).
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.

Sites / Locations

Universitätsklinikum Freiburg
Johannes Gutenberg-Universität Mainz
University Hospital Basel
Clinic of Hematology, Oncology Institute of Southern Switzerland
University Hospital Bern
Hôpitaux Universitaires Genève
Clinica Luganese Moncucco
University Hospital Zurich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Test Group

Control Group

Arm Description

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.

No study drug

Outcomes

Primary Outcome Measures

hospitalizations

all-cause death

Secondary Outcome Measures

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

any hospitalizations

all-cause death

Net clinical benefit

measured by number of cardiovascular events, and major bleeding

Disseminated intravascular coagulation

ISTH criteria, in-hospital diagnosis

Full Information

NCT ID

NCT04400799

First Posted

May 15, 2020

Last Updated

May 17, 2022

Sponsor

University of Zurich

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

1. Study Identification

Unique Protocol Identification Number

NCT04400799

Brief Title

Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With COVID-19

Official Title

Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With Coronavirus: The Multicenter Randomized Controlled Ovid Trial

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Terminated

Why Stopped

due to results from interim analysis

Study Start Date

June 15, 2020 (Actual)

Primary Completion Date

February 7, 2022 (Actual)

Study Completion Date

April 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Zurich

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19, Pulmonary Embolism, Deep Vein Thrombosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

475 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Test Group

Arm Type

Experimental

Arm Description

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.

Arm Title

Control Group

Arm Type

No Intervention

Arm Description

No study drug

Intervention Type

Drug

Intervention Name(s)

Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml

Intervention Description

daily incetion s.c. for 14 days

Primary Outcome Measure Information:

Title

hospitalizations

Time Frame

30 days

Title

all-cause death

Time Frame

30 days

Secondary Outcome Measure Information:

Title

Number of cardiovascular events

Description

Time Frame

within 14 days, 30 days, and 90 days of randomization

Title

any hospitalizations

Time Frame

within 14 days, 30 days, and 90 days of randomization

Title

all-cause death

Time Frame

within 14 days, 30 days, and 90 days of randomization

Title

Net clinical benefit

Description

measured by number of cardiovascular events, and major bleeding

Time Frame

within 14 days, 30 days, and 90 days of enrolment.

Title

Disseminated intravascular coagulation

Description

ISTH criteria, in-hospital diagnosis

Time Frame

within 14 days, 30 days, and 90 days of enrolment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nils Kucher, Prof.

Organizational Affiliation

University of Zurich

Official's Role

Principal Investigator

Facility Information:

Facility Name

Universitätsklinikum Freiburg

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Johannes Gutenberg-Universität Mainz

City

Mainz

ZIP/Postal Code

55122

Country

Germany

Facility Name

University Hospital Basel

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Facility Name

Clinic of Hematology, Oncology Institute of Southern Switzerland

City

Bellinzona

Country

Switzerland

Facility Name

University Hospital Bern

City

Bern

Country

Switzerland

Facility Name

Hôpitaux Universitaires Genève

City

Geneva

Country

Switzerland

Facility Name

Clinica Luganese Moncucco

City

Lugano

Country

Switzerland

Facility Name

University Hospital Zurich

City

Zürich

ZIP/Postal Code

8091

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35779558

Citation

Barco 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.

Results Reference

derived

PubMed Identifier

32907635

Citation

Barco 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.

Results Reference

derived

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Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With COVID-19

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