COVID-HEP: Preventing COVID-19 Complications With Low- and High-dose Anticoagulation

Sponsor

University Hospital, Geneva (Other)

Overall Status

Terminated

CT.gov ID

NCT04345848

Collaborator

(none)

160

Enrollment

Locations

Arms

13.1

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID Sars-CoV2	Drug: Enoxaparin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Preventing COVID-19-associated Thrombosis, Coagulopathy and Mortality With Low- and High-dose Anticoagulation: a Multicentric Randomized, Open-label Clinical Trial

Actual Study Start Date :

Apr 28, 2020

Actual Primary Completion Date :

Jun 2, 2021

Actual Study Completion Date :

Jun 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Therapeutic anticoagulation Participants will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or intravenous unfractionated heparin, from admission until the end of hospital stay or clinical recovery.	Drug: Enoxaparin Two different doses of anticoagulation Other Names: Unfractionated heparin
Active Comparator: Prophylactic anticoagulation Participants will be treated with prophylactic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or unfractionated heparin, from admission until the end of hospital stay or clinical recovery. If hospitalized in the intensive care unit, they will receive an augmented thromboprophylaxis regimen as standard of care.	Drug: Enoxaparin Two different doses of anticoagulation Other Names: Unfractionated heparin

Arm

Intervention/Treatment

Experimental: Therapeutic anticoagulation

Participants will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or intravenous unfractionated heparin, from admission until the end of hospital stay or clinical recovery.

Drug: Enoxaparin

Two different doses of anticoagulation

Other Names:

Unfractionated heparin

Active Comparator: Prophylactic anticoagulation

Participants will be treated with prophylactic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or unfractionated heparin, from admission until the end of hospital stay or clinical recovery. If hospitalized in the intensive care unit, they will receive an augmented thromboprophylaxis regimen as standard of care.

Drug: Enoxaparin

Two different doses of anticoagulation

Other Names:

Unfractionated heparin

Outcome Measures

Primary Outcome Measures

Composite outcome of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality [30 days]
Risk of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality

Secondary Outcome Measures

Arterial thrombosis [30 days]
Risk of ischemic stroke, myocardial infarction and/or limb ischemia
Venous thromboembolism [30 days]
Risk of symptomatic venous thromboembolism or asymptomatic proximal leg deep vein thrombosis
Disseminated intravascular coagulation [30 days]
Risk of DIC
All-cause mortality [30 days]
Risk of all-cause mortality
Sepsis-induced coagulopathy [30 days]
Risk of SIC
Acute respiratory distress syndrome [30 days]
Risk of ARDS
Durations of hospital stay, ICU stay, ventilation [30 days]
Number of days with these care processes
Sequential organ failure assessment score [30 days]
Highest score per participant
Clinical deterioration [30 days]
Risk of clinical deterioration

Other Outcome Measures

Major bleeding [30 days]
Risk of ISTH-defined major bleeding
Clinically relevant non-major bleeding [30 days]
Risk of ISTH-defined CRNMB
Heparin-induced thrombocytopenia [30 days]
Risk of documented HIT
PaO2/FiO2 index [30 days]
Measures of PaO2/FiO2 among participants with mechanical ventilation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Geneva University Hospitals	Geneva	Switzerland
2	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne	Switzerland
3	Ospedale Regionale di Locarno	Locarno	Switzerland
4	Hôpital du Valais	Sion	Switzerland