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

• ClinicalTrials.gov Identifier: NCT04345848
• Recruitment Status: Terminated
• First Posted: April 15, 2020
• Last Update Posted: September 14, 2021
• Sponsor: University Hospital, Geneva
• Information provided by (Responsible Party): Marc Blondon, University Hospital, Geneva

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 (Clinical Trial)
• 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: April 28, 2020
• Actual Primary Completion Date: June 2, 2021
• Actual Study Completion Date: June 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 Name: 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 Name: Unfractionated heparin

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Major bleeding [ Time Frame: 30 days ]
   Risk of ISTH-defined major bleeding
2. Clinically relevant non-major bleeding [ Time Frame: 30 days ]
   Risk of ISTH-defined CRNMB
3. Heparin-induced thrombocytopenia [ Time Frame: 30 days ]
   Risk of documented HIT
4. PaO2/FiO2 index [ Time Frame: 30 days ]
   Measures of PaO2/FiO2 among participants with mechanical ventilation

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Switzerland

Geneva University Hospitals

Geneva, Switzerland

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Switzerland

Ospedale Regionale di Locarno

Locarno, Switzerland

Hôpital du Valais

Sion, Switzerland

Sponsors and Collaborators

University Hospital, Geneva

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Marc Blondon, Attending Physician, Angiology, University Hospital, Geneva
• ClinicalTrials.gov Identifier: NCT04345848
• Other Study ID Numbers: 2020-00794
• First Posted: April 15, 2020
• Last Update Posted: September 14, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Marc Blondon, University Hospital, Geneva:

anticoagulation; heparin; thrombosis

Additional relevant MeSH terms:

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Heparin; Enoxaparin; Calcium heparin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action