PMID- 33823560
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20240328
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 121
IP  - 12
DP  - 2021 Dec
TI  - Treatment-Dose LMWH versus Prophylactic/Intermediate Dose Heparins in High-Risk 
      COVID-19 Inpatients: Rationale and Design of the HEP-COVID Trial.
PG  - 1684-1695
LID - 10.1055/a-1475-2351 [doi]
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 x 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 x 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.
CI  - Thieme. All rights reserved.
FAU - Goldin, Mark
AU  - Goldin M
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
FAU - Giannis, Dimitrios
AU  - Giannis D
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
FAU - Diab, Wassim
AU  - Diab W
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
FAU - Wang, Janice
AU  - Wang J
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
FAU - Khanijo, Sameer
AU  - Khanijo S
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
FAU - Sharifova, Gulru
AU  - Sharifova G
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
FAU - Cohen, Marc
AU  - Cohen M
AD  - Department of Medicine, Newark Beth Israel Medical Center, Newark, New Jersey, 
      United States.
FAU - Lund, Jeet M
AU  - Lund JM
AD  - Wellspan York Hospital, York, Pennsylvania, United States.
FAU - Mignatti, Andrea
AU  - Mignatti A
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
AD  - Department of Cardiology, Lenox Hill Hospital, Northwell Health, New York, New 
      York, United States.
FAU - Gianos, Eugenia
AU  - Gianos E
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
AD  - Department of Cardiology, Lenox Hill Hospital, Northwell Health, New York, New 
      York, United States.
FAU - Tafur, Alfonso
AU  - Tafur A
AD  - Department of Medicine and Vascular Medicine, NorthShore University Health 
      System, Evanston, Illinois, United States.
AD  - Division of Cardiology, University of Chicago, Pritzker School of Medicine, 
      Chicago, Illinois, United States.
FAU - Lewis, Paul A
AU  - Lewis PA
AD  - Evidence Based Medicine, Baycare Health System, Clearwater, Florida, United 
      States.
FAU - Cohoon, Kevin
AU  - Cohoon K
AD  - Division of Cardiovascular Medicine, Department of Medicine, Froedtert and 
      Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
FAU - Kittelson, John M
AU  - Kittelson JM
AD  - Department of Biostatistics and Informatics, Colorado School of Public Health, 
      University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
FAU - Lesser, Martin L
AU  - Lesser ML
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
FAU - Sison, Cristina P
AU  - Sison CP
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
FAU - Rahman, Husneara
AU  - Rahman H
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
FAU - Ochani, Kanta
AU  - Ochani K
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
FAU - Hiatt, William R
AU  - Hiatt WR
AD  - Biostatistics, Colorado Prevention Center (CPC) Clinical Research, Aurora, 
      Colorado, United States.
AD  - Division of Cardiology, University of Colorado, School of Medicine, Aurora, 
      Colorado, United States.
FAU - Dale, Rita A
AU  - Dale RA
AD  - Biostatistics, Colorado Prevention Center (CPC) Clinical Research, Aurora, 
      Colorado, United States.
FAU - Anderson, Victoria E
AU  - Anderson VE
AD  - Biostatistics, Colorado Prevention Center (CPC) Clinical Research, Aurora, 
      Colorado, United States.
FAU - Bonaca, Marc
AU  - Bonaca M
AD  - Biostatistics, Colorado Prevention Center (CPC) Clinical Research, Aurora, 
      Colorado, United States.
AD  - Division of Cardiology, University of Colorado, School of Medicine, Aurora, 
      Colorado, United States.
FAU - Halperin, Jonathan L
AU  - Halperin JL
AD  - Department of Cardiovascular Medicine, The Cardiovascular Institute, Mount Sinai 
      Medical Center, New York, New York, United States.
FAU - Weitz, Jeffrey I
AU  - Weitz JI
AD  - Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
AD  - Department of Biochemistry and Biomedical Sciences, McMaster University, 
      Hamilton, Ontario, Canada.
AD  - Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
FAU - Spyropoulos, Alex C
AU  - Spyropoulos AC
AD  - Institute of Health Innovations and Outcomes Research, The Feinstein Institutes 
      for Medical Research, Northwell Health, Manhasset, New York, United States.
AD  - Department of Medicine, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Hempstead, New York, United States.
LA  - eng
PT  - Clinical Trial Protocol
PT  - Journal Article
DEP - 20210528
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
SB  - IM
MH  - Humans
MH  - *Anticoagulants/administration & dosage/adverse effects
MH  - Clinical Trials, Phase III as Topic
MH  - *COVID-19/complications/diagnosis
MH  - *COVID-19 Drug Treatment
MH  - *Enoxaparin/administration & dosage/adverse effects
MH  - Pragmatic Clinical Trials as Topic
MH  - Prospective Studies
MH  - Risk Assessment
MH  - Risk Factors
MH  - *Thromboembolism/diagnosis/drug therapy/etiology
MH  - Time Factors
MH  - Treatment Outcome
MH  - United States
MH  - Venous Thromboembolism/diagnosis/etiology/prevention & control
MH  - Multicenter Studies as Topic
COIS- M.G.: research grant from Janssen; M.C.: speakers bureau Sanofi; A.T.: 
      educational grant: Janssen, research grant: Janssen, Bristol Meyers Squibb, 
      Idorsia, consultant: Recovery Force, J.M.K.: consultant for Bayer Healthcare, 
      Jansen, the ATLAS Group, AMAG pharmaceuticals, Agile Therapeutics for advisory 
      and steering committee activities. Data and safety monitoring committees for 
      Cystic Fibrosis Foundation Therapeutics, Novo Nordisk, Pfizer, Genentech, and 
      BioMarin pharmaceuticals. M.B.: research grant support to CPC Clinical Research 
      from Amgen, AstraZeneca, Bayer, Janssen, Merck, NovoNordisk; J.L.H.: 
      consultancies with the ATLAS Group, Bayer Healthcare, Boehringer Ingelheim, and 
      Population Health Research Institute; J.I.W.: consultant for Anthos, ATLAS Group, 
      Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Ionis, 
      Janssen, Johnson and Johnson, Merck, Pfizer, PhaseBio, and Servier, institutional 
      research grants from Bayer and Boehringer Ingelheim; A.C.S.: Janssen, Boehringer 
      Ingelheim, Bayer, BMS, Portola, ATLAS Group: consultancy; Janssen, Boehringer 
      Ingelheim: research funding. D.G., W.D., J.W., S.K., G.S., J.M.L., A.M., E.G., 
      P.A.L., K.C., M.L., C.P.S., H.R., K.O., W.R.H., R.A.D., V.E.A.: no conflict of 
      interest.
EDAT- 2021/04/07 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/04/06 20:23
PHST- 2021/04/06 00:00 [aheadofprint]
PHST- 2021/04/07 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/04/06 20:23 [entrez]
AID - 10.1055/a-1475-2351 [doi]
PST - ppublish
SO  - Thromb Haemost. 2021 Dec;121(12):1684-1695. doi: 10.1055/a-1475-2351. Epub 2021 
      May 28.