TY - JOUR
T1 - Treatment-Dose LMWH versus Prophylactic/Intermediate Dose Heparins in High-Risk COVID-19 Inpatients
T2 - Rationale and Design of the HEP-COVID Trial
AU - Goldin, Mark
AU - Giannis, Dimitrios
AU - Diab, Wassim
AU - Wang, Janice
AU - Khanijo, Sameer
AU - Sharifova, Gulru
AU - Cohen, Marc
AU - Lund, Jeet M.
AU - Mignatti, Andrea
AU - Gianos, Eugenia
AU - Tafur, Alfonso
AU - Lewis, Paul A.
AU - Cohoon, Kevin
AU - Kittelson, John M.
AU - Lesser, Martin L.
AU - Sison, Cristina P.
AU - Rahman, Husneara
AU - Ochani, Kanta
AU - Hiatt, William R.
AU - Dale, Rita A.
AU - Anderson, Victoria E.
AU - Bonaca, Marc
AU - Halperin, Jonathan L.
AU - Weitz, Jeffrey I.
AU - Spyropoulos, Alex C.
N1 - Publisher Copyright:
© 2021 Royal Society of Chemistry. All rights reserved.
PY - 2021/5/28
Y1 - 2021/5/28
N2 - Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.
AB - Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.
KW - D-dimer
KW - arterial thromboembolism
KW - coronavirus disease-2019
KW - thromboprophylaxis
KW - venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85107294216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107294216&partnerID=8YFLogxK
U2 - 10.1055/a-1475-2351
DO - 10.1055/a-1475-2351
M3 - Article
C2 - 33823560
AN - SCOPUS:85107294216
SN - 0340-6245
VL - 121
SP - 1684
EP - 1695
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 12
ER -