Anticoagulation in Critically Ill Patients With COVID-19... | NCT04406389

Anticoagulation in Critically Ill Patients With COVID-19... | NCT04406389 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Intermediate Dose Prophylaxis	Active Comparator	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously	Drug: Enoxaparin sodium Drug: Unfractionated heparin Drug: Fondapariniux
Therapeutic Dose Anticoagulation	Experimental	Subjects will receive one of the following interventions, at their physician's discretion: Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol). Enoxaparin 1 mg/kg subcutaneously every 12 hours Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol. Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight: ≥100 kg: 10 mg daily <100 kg but ≥50 kg: 7.5 mg daily <50 kg: 5 mg daily	Drug: Enoxaparin sodium Drug: Unfractionated heparin Drug: Fondapariniux Drug: Argatroban

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Enoxaparin sodium	Drug	Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours

Outcomes Module

Measure	Description	Time Frame
30-day Mortality	Comparison of number of COVID-19 positive patients who have died within 30 days of starting treatment on each treatment arm	30 days

Secondary Outcomes

Measure	Description	Time Frame
Length of Intensive Care Unit (ICU) Stay in Days	Comparison of length of ICU stay in days between each treatment arm.	6 months
Number of Documented Venous Thromboembolism (VTE), Arterial Thrombosis (Stroke, Myocardial Infarction, Other) and Microthrombosis Events

Contacts/Locations Module

Name	Affiliation	Role
Maria T DeSancho, MD, MSc	Weill Medical College of Cornell University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
New York Presbyterian Brooklyn Methodist Hospital		Brooklyn	New York	11215	United States
Weill Cornell Medicine

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32073213	Background	Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
32220112	Background	Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 May;18(5):1094-1099. doi: 10.1111/jth.14817. Epub 2020 Apr 27.

Arm/Group Information

ID	Title	Description
FG000	Intermediate Dose Prophylaxis	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily
FG001	Therapeutic Dose Anticoagulation	Subjects will receive one of the following interventions, at their physician's discretion: Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol). Enoxaparin 1 mg/kg subcutaneously every 12 hours Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol. Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight: 100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min, OR 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: ≥100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Argatroban: Therapeutic Dose Anticoagulation Arm: Dosed according to institutional protocol

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0004 subjects FG00110 subjects
COMPLETED		FG0004 subjects FG00110 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Intermediate Dose Prophylaxis	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

30-day Mortality

Comparison of number of COVID-19 positive patients who have died within 30 days of starting treatment on each treatment arm

Posted

Count of Participants

Participants

30 days

ID	Title	Description
OG000	Intermediate Dose Prophylaxis	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intermediate Dose Prophylaxis	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Adult Respiratory Distress Syndrome	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Heart Failure	Cardiac disorders	CTCAE (Unspecified)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Dr. Maria T. DeSancho	Weill Cornell Medicine	646-962-2065		mtd2002@med.cornell.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 3, 2021	Aug 24, 2023	Prot_SAP_000.pdf

Condition Browse Module

ID	Term
D000086382	COVID-19

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections

Intervention Browse Module

ID	Term
C000711671	enoxaparin sodium
D017984	Enoxaparin
D006493	Heparin
D000077425	Fondaparinux
C031942	argatroban

ID	Term
D006495	Heparin, Low-Molecular-Weight
D006025	Glycosaminoglycans
D011134	Polysaccharides
D002241	Carbohydrates

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0011 BG0021
Not Hispanic or Latino	BG0001 BG0017 BG0028
Unknown or Not Reported	BG0003 BG0012 BG0025

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020
Asian	BG0000 BG0010 BG0020
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020
Black or African American	BG0000 BG0012 BG0022
White	BG0003 BG0015 BG0028
More than one race	BG0000 BG0010 BG0020
Unknown or Not Reported	BG0001 BG0013 BG0024

Respiratory Support at Time of Randomization

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
High Flow Nasal Cannula or Non-Invasive Ventilation (>15 L/min)	BG0001 BG0016 BG0027
Invasive Mechanical Ventilation or ECMO	BG0001 BG0012 BG0023
Supplemental Oxygen (<15L/min)	BG0002 BG0012 BG0024

Vasopressor Support at Time of Randomization

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Subjects on Vasopressor Support	BG0000 BG0012 BG0022
Subjects not on Vasopressor Support	BG0004 BG0018 BG00212

Secondary

Length of Intensive Care Unit (ICU) Stay in Days

Comparison of length of ICU stay in days between each treatment arm.

This outcome measure is only assessing participants that had an ICU stay while participating in the study. Participants that never had an ICU stay are excluded from the analysis.

Posted

Median

Full Range

Days

6 months

ID	Title	Description
OG000	Intermediate Dose Prophylaxis	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily
OG001	Therapeutic Dose Anticoagulation	Subjects will receive one of the following interventions, at their physician's discretion: Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol). Enoxaparin 1 mg/kg subcutaneously every 12 hours Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol. Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight: 100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min, OR 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: ≥100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Argatroban: Therapeutic Dose Anticoagulation Arm: Dosed according to institutional protocol

Units	Counts
Participants	OG0002 OG0016

Title

Denominators

Categories

Title	Measurements
	OG00025.5(10 to 41) OG00125(15 to 111)

Secondary

Number of Documented Venous Thromboembolism (VTE), Arterial Thrombosis (Stroke, Myocardial Infarction, Other) and Microthrombosis Events

Comparison of number of documented VTE, arterial thrombosis and microthrombosis events on each treatment arm

Posted

Number

Count of Events

6 months

ID	Title	Description
OG000	Intermediate Dose Prophylaxis	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily
OG001	Therapeutic Dose Anticoagulation	Subjects will receive one of the following interventions, at their physician's discretion: Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol). Enoxaparin 1 mg/kg subcutaneously every 12 hours Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol. Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight: 100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min, OR 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: ≥100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Argatroban: Therapeutic Dose Anticoagulation Arm: Dosed according to institutional protocol

Units	Counts
Participants	OG0004 OG00110

Title

Denominators

Categories

Venous Thromboembolism Events

Title	Measurements
	OG0001 OG0010

Arterial Thrombosis Events

Title	Measurements
	OG000

Secondary

Number of Major and Clinically Relevant Non-major Bleeding Events

Comparison of major and clinically-relevant non-major bleeding events on each treatment arm, as defined by the International Society of Thrombosis and Haemostasis (ISTH) criteria.

Posted

Number

Count of Events

6 months

ID	Title	Description
OG000	Intermediate Dose Prophylaxis	Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily
OG001	Therapeutic Dose Anticoagulation	Subjects will receive one of the following interventions, at their physician's discretion: Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol). Enoxaparin 1 mg/kg subcutaneously every 12 hours Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol. Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight: 100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Enoxaparin sodium: Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min, OR 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours Unfractionated heparin: Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol Fondapariniux: Intermediate Dose Prophylaxis Arm: 2.5mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: ≥100kg: 10 mg daily <100kg but ≥50 kg: 7.5 mg daily <50kg: 5 mg daily Argatroban: Therapeutic Dose Anticoagulation Arm: Dosed according to institutional protocol

Units	Counts
Participants	OG0004 OG00110

Title

Denominators

Categories

Major Bleeding Events

Title	Measurements
	OG0001 OG0011

Clinically Relevant Non-Major Bleeding Events

Title	Measurements
	OG000