Clinical trial NCT04345848: Preventing COVID-19 Complications With Low- and High-dose Anticoagulation
Official title: Preventing COVID-19-associated Thrombosis, Coagulopathy and Mortality With Low- and High-dose Anticoagulation: a Multicentric Randomized, Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID
Sars-CoV2
Keywords: anticoagulation
heparin
thrombosis
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2020-04-15
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The ongoing COVID-19 pandemic affects millions of humans worldwide and has led to thousands of acute medical hospitalizations. There is evidence that hospitalized cases often suffer from an important infection-related coagulopathy and from elevated risks of thrombosis. Anticoagulants may have positive effects here, to reduce the burden of thrombotic disease and the hyperactivity of coagulation, and may also hold beneficial anti-inflammatory effects against sepsis and the development of ARDS.

The investigators hypothesize that high-dose anticoagulants, compared with low-dose anticoagulants, lower the risk of venous and arterial thrombosis, disseminated intravascular coagulation (DIC) and mortality. This open-label controlled trial will randomize hospitalized adults with severe COVID-19 infection to therapeutic anticoagulation vs. thromboprophylaxis during the hospital stay.


Eligibility criteria: Inclusion Criteria: adult patient with COVID-19 infections, admitted to:

* an acute non-critical medical ward with admission D-dimer levels \>1,000ng/mL, or
* an acute critical ward (ICU, intermediate care unit)

Exclusion Criteria:

* ongoing or planned therapeutic anticoagulation for any other indication
* contra-indication to therapeutic anticoagulation
* hypersensitivity to heparin
* personal history of heparin-induced thrombocytopenia
* suspected or confirmed bacterial endocarditis
* bleeding events or tendency due to a suspected or confirmed hemostatic bleeding disorder
* organic lesion prone to bleeding
* platelet count \<50G/L, Hb level \<80g/L
* ongoing or recent (\<30 days) major bleeding, ischemic stroke, trauma, surgery
* use of dual antiplatelet therapy
* pregnancy
* bodyweight \<40kg or \>150kg.
* end of life care setting
* unwillingness to consent
* ongoing participation in a COVID-19 randomized clinical trial testing another therapeutic intervention

Primary outcomes:
measure: Composite outcome of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality
timeFrame: 30 days
Secondary outcomes:
measure: Arterial thrombosis
timeFrame: 30 days
measure: Venous thromboembolism
timeFrame: 30 days
measure: Disseminated intravascular coagulation
timeFrame: 30 days
measure: All-cause mortality
timeFrame: 30 days
measure: Sepsis-induced coagulopathy
timeFrame: 30 days
measure: Acute respiratory distress syndrome
timeFrame: 30 days
measure: Durations of hospital stay, ICU stay, ventilation
timeFrame: 30 days
measure: Sequential organ failure assessment score
timeFrame: 30 days
measure: Clinical deterioration
timeFrame: 30 days
Other outcomes:
measure: Major bleeding
timeFrame: 30 days
measure: Clinically relevant non-major bleeding
timeFrame: 30 days
measure: Heparin-induced thrombocytopenia
timeFrame: 30 days
measure: PaO2/FiO2 index
timeFrame: 30 days
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
city: Locarno
country: Switzerland
facility: Ospedale Regionale di Locarno
city: Sion
country: Switzerland
facility: Hôpital du Valais
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.