Trial Outcomes & Findings for Full Dose Heparin Vs. Prophylactic Or Intermediate Dose Heparin in High Risk COVID-19 Patients (NCT NCT04401293)
NCT ID: NCT04401293
Last Updated: 2021-11-22
Results Overview
Risk of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Day 30 ± 2 days.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
257 participants
Primary outcome timeframe
Day 30 ± 2 days
Results posted on
2021-11-22
Participant Flow
Participant milestones
| Measure |
Full Dose LMWH Anticoagulation Therapy
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Overall Study
STARTED
|
130
|
127
|
|
Overall Study
COMPLETED
|
129
|
124
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
Full Dose LMWH Anticoagulation Therapy
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
Baseline Characteristics
Full Dose Heparin Vs. Prophylactic Or Intermediate Dose Heparin in High Risk COVID-19 Patients
Baseline characteristics by cohort
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=129 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=124 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
Total
n=253 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Age in Years
|
65.8 years
STANDARD_DEVIATION 13.9 • n=5 Participants
|
67.7 years
STANDARD_DEVIATION 14.1 • n=7 Participants
|
66.7 years
STANDARD_DEVIATION 14.00 • n=5 Participants
|
|
Sex/Gender, Customized
Male
|
68 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
136 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
61 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
117 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
33 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
56 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
102 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
29 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 30 ± 2 daysRisk of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Day 30 ± 2 days.
Outcome measures
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=129 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=124 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Composite Outcome of Arterial Thromboembolic Events, Venous Thromboembolic Events and All-cause Mortality at Day 30 ± 2 Days.
|
25 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Day 30 ± 2 daysRisk of major bleeding defined using the International Society of Thrombosis and Haemostasis (ISTH) criteria
Outcome measures
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=129 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=124 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Major Bleeding
|
6 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 10 + 4The composite of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Hospital Day 10 + 4
Outcome measures
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=129 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=124 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Composite Outcome of Arterial Thromboembolic Events, Venous Thromboembolic Events and All-cause Mortality at Hospital Day 10 + 4
|
2 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Day 30 ± 2 days.Population: COVID-19 patients have been noted to have significantly elevated markers of hypercoagulability including d-dimer (Dd), fibrinogen levels, FVIII levels, short activated partial thromboplastin time (aPTT) and Sepsis-Induced Coagulopathy (SIC) scores with an increase in venous thromboembolic disease as well as cardiac injury.
Sepsis-induced coagulopathy (SIC) score predicts likelihood of sepsis-induced coagulopathy based on ISTH guidelines. The score uses the following domains: * Platelets, K/uL (thousands per microliter) * INR (International Normalized Ratio) * D-Dimer Level * Fibrinogen Platelet count \> 100 cells x 10\^9/L is 0 points, platelet count 50 to 100 cells x 10\^9/L is 1 point and Platelet count \< 50 cells x 10\^9/L is 2 points. INR \< 1.3 is 0 points, INR 1.3 to 1.7 is 1 point and INR \> 1.7 is 2 points. D-Dimer level \< 400 ng/mL is 0 points, D-Dimer level 400-4000 ng/mL is 2 points and D-Dimer level \> 4000 ng/mL is 3 points. Fibrinogen level \> 100 mg/dL is 0 points and fibrinogen level \< 100 mg/dL is 1 point. Calculated (SIC) scores yields a possible 0 to 6 points, where ≥4 predicts higher mortality rates within 30 days and greater risk of pulmonary embolism.
Outcome measures
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=129 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=124 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Sepsis-induced Coagulopathy (SIC) Score
|
2.35 units on a scale
Standard Deviation 0.73
|
2.31 units on a scale
Standard Deviation 0.85
|
SECONDARY outcome
Timeframe: Day 30 ± 2 days.Progression to Acute Respiratory Distress Syndrome (ARDS) based on monitoring of patient conditions.
Outcome measures
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=127 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=121 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Progression to Acute Respiratory Distress Syndrome (ARDS)
|
11 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Day 30 ± 2 days.Need for Intubation will be based on monitoring of patient conditions.
Outcome measures
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=122 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=121 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Need for Intubation
|
17 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Day 30 ± 2 days.Need for Re-hospitalization will be based on monitoring of patient conditions.
Outcome measures
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=129 Participants
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=124 Participants
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Re-hospitalization
|
1 Participants
|
3 Participants
|
Adverse Events
Full Dose LMWH Anticoagulation Therapy
Serious events: 2 serious events
Other events: 0 other events
Deaths: 25 deaths
Prophylactic/Intermediate Dose LMWH or UFH Therapy
Serious events: 0 serious events
Other events: 0 other events
Deaths: 31 deaths
Serious adverse events
| Measure |
Full Dose LMWH Anticoagulation Therapy
n=129 participants at risk
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and \< 30ml/min) during the course of their hospitalization.
Enoxaparin: Full Dose LMWH anticoagulation therapy
|
Prophylactic/Intermediate Dose LMWH or UFH Therapy
n=124 participants at risk
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Prophylactic/Intermediate Dose Enoxaparin: Prophylactic/Intermediate Dose LMWH or UFH therapy
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.6%
2/129 • Number of events 2 • From screening/randomization, adverse event data was monitored and collected for each participant for 30 days (± 2 days), which was their duration in the study.
|
0.00%
0/124 • From screening/randomization, adverse event data was monitored and collected for each participant for 30 days (± 2 days), which was their duration in the study.
|
Other adverse events
Adverse event data not reported
Additional Information
Alex Spyropoulos, MD
System Director - Anticoagulation and Clinical Thrombosis Services Northwell Health at Lenox Hill Hospital Affiliation: Northwell Health
Phone: (212) 434-6776
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place