Clinical trial NCT04366960: Comparison of Two Doses of Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Covid19
Keywords: COVID19
Lead sponsor: Niguarda Hospital
Sponsor class: OTHER
First posted: 2020-04-29
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* All-comers patients aged \>=18 years and admitted to hospital with laboratory-confirmed SARS-CoV-2 infection

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Incidence of venous thromboembolism detected by imaging
timeFrame: 30 days
Secondary outcomes:
measure: In hospital major complications
timeFrame: 30 days
measure: Number of deep venous thrombosis events
timeFrame: 30 days
measure: Sequential organ failure assessment
timeFrame: 30 days
measure: C-reactive protein
timeFrame: 30 days
measure: Interleukin-6
timeFrame: 30 days
measure: D-dimer
timeFrame: 30 days
measure: hs-troponin levels
timeFrame: 30 days
measure: Acute Respiratory Distress Syndrome
timeFrame: 30 days
measure: Hospital stay
timeFrame: 30 days
measure: Right ventricular function
timeFrame: 30 days
measure: Number of pulmonary embolism events
timeFrame: 30 days
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Study officials:
References:
citation: 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. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
citation: Flumignan 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.
citation: Levi 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.