Covid19Phase 3X-Covid 19NCT04366960
Comparison of Two Doses of Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients
A Phase 3 study testing Enoxaparin in people with Covid19, run by Niguarda Hospital at 1 site in Italy.
Trial summary
The purpose of this study is to determine whether a higher dose of low molecular weight heparin (enoxaparin 40 mg b.i.d.) is superior than the standard prophylaxis dose (enoxaparin 40 mg o.d.) in reducing thromboembolic events in COVID-19 patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Enoxaparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 189 participants
- Where
- 1 siteItaly
- Study dates
- 14 May 2020to 25 May 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All-comers patients aged >=18 years and admitted to hospital with laboratory-confirmed SARS-CoV-2 infection
Who cannot join
- Patients admitted directly to an intensive care unit;
- Estimated creatinine clearance <15 ml/min/1.73m2;
- Patients needing anticoagulant for prior indication;
- Participants involved in other clinical trials;
- Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, 20162
About this study
Official title: Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients: Comparison of 40 mg o.d. Versus 40 mg b.i.d. A Randomized Clinical Trial
The purpose of this study is to determine whether a higher dose of low molecular weight heparin (enoxaparin 40 mg b.i.d.) is superior than the standard prophylaxis dose (enoxaparin 40 mg o.d.) in reducing thromboembolic events in COVID-19 patients.
Read the detailed description
Coronavirus disease-19 (COVID-19 ), which is caused by SARS-CoV-2 infection, are apparently at high risk of venous thromboembolism (VTE), as a consequence of activation of the hemostatic system which, in the most severe cases, can also be associated with the formation of microthrombi and clinically relevant disseminated intravascular coagulation. Concerns about the efficacy of thromboprophylaxis with standard doses of low-molecular-weight heparin (LMWH) has been raised. Therefore, LMWH at higher doses than those recommended for thromboprophylaxis is used in some hospitals, although no evidence exists yet of higher efficacy of high doses compared to standard prophylactic doses. This practice might as well increase the risk of major bleeding. The investigators designed a randomized trial comparing standard prophylactic dose of subcutaneous enoxaparin (40 mg o.d.) with higher dose (40 mg b.i.d) with the aim of testing whether high-dose thromboprophylaxis is more effective than standard dose in preventing VTE in COVID-19 patients.
- Conditions
- Covid19
- Being tested
- Enoxaparin
- Keywords
- COVID19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnoxaparinDrug
Subcutaneous enoxaparin
| Study group | Role | What they receive |
|---|---|---|
| 40 mg subcutaneous enoxaparin o.d. | Active comparator | Effects of 40 mg subcutaneous enoxaparin o.d. Receives: Drug: Enoxaparin |
| 40 mg subcutaneous enoxaparin b.i.d | Active comparator | Effects of 40 mg subcutaneous enoxaparin b.i.d Receives: Drug: Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of venous thromboembolism detected by imaging
Deep vein thrombosis events diagnosed by serial compression ultrasonography and pulmonary embolism events diagnosed by computed tomography scan
Measured: 30 days
Secondary outcomes (11)
In hospital major complications
death, venous thromboembolism, use of mechanical ventilation, stroke, acute myocardial infarction and admission to an intensive care
Measured: 30 days
Number of deep venous thrombosis events
Deep venous thrombosis events diagnosed by serial compression ultrasonography
Measured: 30 days
Sequential organ failure assessment
Maximum sequential organ failure assessment (SOFA) score comparison between the two groups.
The SOFA score ranges from 0 to 24. Higher SOFA score is associated with a greater risk of death or prolonged intensive care unit stay.
Measured: 30 days
C-reactive protein
To compare C-reactive protein levels as % above the upper reference limit [URL]) among the two groups.
Measured: 30 days
Interleukin-6
To compare Interleukin-6 levels as % above the upper reference limit [URL]) among the two groups.
Measured: 30 days
D-dimer
To D-dimer compare levels as % above the upper reference limit [URL]) among the two groups.
Measured: 30 days
hs-troponin levels
To compare hs-troponin levels as % above the upper reference limit [URL]) among the two groups.
Measured: 30 days
Acute Respiratory Distress Syndrome
To compare the incidence of SARS-CoV-2-related Acute Respiratory Distress Syndrome (ARDS) between the two groups.
Measured: 30 days
Hospital stay
To compare length of hospital stay between the two groups.
Measured: 30 days
Right ventricular function
To compare measures of right ventricular function at trans-thoracic echocardiography or CT between admission and follow-up, whenever available
Measured: 30 days
Number of pulmonary embolism events
Pulmonary embolism events diagnosed by computed tomography scan
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2020
- Study start14 May 2020
- Primary completion25 May 2021
- Study completion25 May 2021
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 Covid19Studies of the same condition, open and under way.
- 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
- Model description
- Open-label Multicentre Prospective Controlled Randomized Trial in patients with SARS-CoV-2 infection. Patients will be randomized 1:1 to 40 mg subcutaneous enoxaparin o.d. versus 40 mg enoxaparin b.i.d within 12 hours after hospitalization.
- Masking
- None (open label)
- Enrolment
- 189 participants (actual)
Sponsor and investigators
- Lead sponsor
- Niguarda Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04366960
- Sponsor's protocol ID
- 2020-001708-41
- Acronym
- X-Covid 19
- Status last verified
- Jun 2021
- First submitted
- 24 Apr 2020
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
PubMed 35244208Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.
PubMed 33502773Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020 Jun;7(6):e438-e440. doi: 10.1016/S2352-3026(20)30145-9. Epub 2020 May 11. No abstract available.
PubMed 32407672
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients: Comparison of 40 mg o.d. Versus 40 mg b.i.d. A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04366960
- Acronym / sponsor ID
- X-Covid 19 / 2020-001708-41
- Conditions
- Covid19
- Keywords
- COVID19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 189 participants (actual)
- Lead sponsor
- Niguarda HospitalUniversity, hospital or other
- Study start
- 14 May 2020 (actual)
- Primary completion
- 25 May 2021 (actual)
- Study completion
- 25 May 2021 (actual)
- First posted
- 29 Apr 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 purpose of this study is to determine whether a higher dose of low molecular weight heparin (enoxaparin 40 mg b.i.d.) is superior than the standard prophylaxis dose (enoxaparin 40 mg o.d.) in reducing thromboembolic events in COVID-19 patients.
Detailed description
Coronavirus disease-19 (COVID-19 ), which is caused by SARS-CoV-2 infection, are apparently at high risk of venous thromboembolism (VTE), as a consequence of activation of the hemostatic system which, in the most severe cases, can also be associated with the formation of microthrombi and clinically relevant disseminated intravascular coagulation. Concerns about the efficacy of thromboprophylaxis with standard doses of low-molecular-weight heparin (LMWH) has been raised. Therefore, LMWH at higher doses than those recommended for thromboprophylaxis is used in some hospitals, although no evidence exists yet of higher efficacy of high doses compared to standard prophylactic doses. This practice might as well increase the risk of major bleeding. The investigators designed a randomized trial comparing standard prophylactic dose of subcutaneous enoxaparin (40 mg o.d.) with higher dose (40 mg b.i.d) with the aim of testing whether high-dose thromboprophylaxis is more effective than standard dose in preventing VTE in COVID-19 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open-label Multicentre Prospective Controlled Randomized Trial in patients with SARS-CoV-2 infection. Patients will be randomized 1:1 to 40 mg subcutaneous enoxaparin o.d. versus 40 mg enoxaparin b.i.d within 12 hours after hospitalization.
| Arm | Type | Receives |
|---|---|---|
| 40 mg subcutaneous enoxaparin o.d. | Active comparator | Drug: EnoxaparinEffects of 40 mg subcutaneous enoxaparin o.d. |
| 40 mg subcutaneous enoxaparin b.i.d | Active comparator | Drug: EnoxaparinEffects of 40 mg subcutaneous enoxaparin b.i.d |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All-comers patients aged >=18 years and admitted to hospital with laboratory-confirmed SARS-CoV-2 infection
Key exclusion criteria (5 listed)
- Patients admitted directly to an intensive care unit;
- Estimated creatinine clearance <15 ml/min/1.73m2;
- Patients needing anticoagulant for prior indication;
- Participants involved in other clinical trials;
- Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
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 |
|---|---|---|
| EnoxaparinSubcutaneous enoxaparin | Drug | 40 mg subcutaneous enoxaparin b.i.d, 40 mg subcutaneous enoxaparin o.d. |
Primary outcome
Incidence of venous thromboembolism detected by imaging
Time frame: 30 days
Deep vein thrombosis events diagnosed by serial compression ultrasonography and pulmonary embolism events diagnosed by computed tomography scan
11 secondary outcomes
In hospital major complications
Time frame: 30 days
Number of deep venous thrombosis events
Time frame: 30 days
Sequential organ failure assessment
Time frame: 30 days
C-reactive protein
Time frame: 30 days
Interleukin-6
Time frame: 30 days
D-dimer
Time frame: 30 days
hs-troponin levels
Time frame: 30 days
Acute Respiratory Distress Syndrome
Time frame: 30 days
Hospital stay
Time frame: 30 days
Right ventricular function
Time frame: 30 days
Number of pulmonary embolism events
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Derived from this study: PubMed 35244208Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
- Derived from this study: PubMed 33502773Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.
- Derived from this study: PubMed 32407672Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020 Jun;7(6):e438-e440. doi: 10.1016/S2352-3026(20)30145-9. Epub 2020 May 11. No abstract available.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enoxaparin in people with Covid19, run by Niguarda Hospital at 1 site in Italy.
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 1 inclusion and 5 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: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of venous thromboembolism detected by imaging (time frame: 30 days). 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 NCT04366960, 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 8 Jun 2021.