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

NCT04345848 | Terminated Phase 3 DMC

• 1 other identifier: 2020-00794
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 4

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.

Conditions

COVID; Sars-CoV2

Keywords

anticoagulation; heparin; thrombosis

Outcome Measures

Primary Outcomes (1)

• Composite outcome of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality

  Risk of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality

  30 days

Secondary Outcomes (9)

• Arterial thrombosis

  30 days

• Venous thromboembolism

  30 days

• Disseminated intravascular coagulation

  30 days

• All-cause mortality

  30 days

• Sepsis-induced coagulopathy

  30 days

Other Outcomes (4)

• Major bleeding

  30 days

• Clinically relevant non-major bleeding

  30 days

• Heparin-induced thrombocytopenia

  30 days

Study Arms (2)

Therapeutic anticoagulation

EXPERIMENTAL

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

Prophylactic anticoagulation

ACTIVE COMPARATOR

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

Interventions

Enoxaparin DRUG

Two different doses of anticoagulation

Also known as: Unfractionated heparin

Prophylactic anticoagulation; Therapeutic anticoagulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (4)

Geneva University Hospitals

Geneva, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Switzerland

Location

Ospedale Regionale di Locarno

Locarno, Switzerland

Location

Hôpital du Valais

Sion, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 35244208 DERIVED

• 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.

  PMID: 33502773 DERIVED

• 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.

  PMID: 32407672 DERIVED

MeSH Terms

Conditions

Thrombosis

Interventions

Enoxaparin; Heparin

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician, Angiology

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 15, 2020
• Study Start: April 28, 2020
• Primary Completion: June 2, 2021
• Study Completion: June 2, 2021
• Last Updated: September 14, 2021

Record last verified: 2021-09

Locations

CH (4)