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A Randomized Trial of Anticoagulation Strategies in COVID-19

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ClinicalTrials.gov Identifier: NCT04359277
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date  ICMJE April 20, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE April 21, 2020
Estimated Primary Completion Date April 21, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2020)
Composite incidence of: all-cause mortality, cardiac arrest, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, stroke, or shock [ Time Frame: 30 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • All-cause mortality [ Time Frame: 1 year ]
  • Incidence of Cardiac Arrest [ Time Frame: 21 days ]
  • Incidence of symptomatic Deep Venous Thrombosis [ Time Frame: 21 days ]
  • Incidence of Pulmonary Embolism [ Time Frame: 21 days ]
  • Incidence of Arterial thromboembolism [ Time Frame: 21 days ]
  • Incidence of myocardial infarction [ Time Frame: 21 days ]
  • Incidence of hemodynamic shock [ Time Frame: 21 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2020)
  • Score on WHO Ordinal Scale [ Time Frame: 30 days ]
    0 = Uninfected; no viral RNA detected Ambulatory
    1. = Asymptomatic; viral RNA detected
    2. = Symptomatic: Independent
    3. = Symptomatic: assistance needed Hospitalized: Mild disease
    4. = Hospitalized; no oxygen therapy
    5. = Hospitalized; oxygen by mask or nasal prongs
    6. = Hospitalized; oxygen by NIV or High flow
    7. = Intubation & Mechanical ventilation, pO2/FIO2 >/= 150 or SpO2/FIO2
    8. = Mechanical ventilation pO2/FIO2 <
    150 (SpO2/FIO2 <200) 9 = Mechanical ventilation pO2/FIO2 < 150 and vasopressors, dialysis 10 = Dead N (%)
  • Incidence of acute kidney injury (KDIGO criteria for Acute Kidney Injury (AKI)) [ Time Frame: 30 days ]
    AKI is defined as any of the following (Not Graded):
    • Increase in SCr by X0.3 mg/dl (X26.5 lmol/l) within 48 hours; or
    • Increase in SCr to X1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or- Urine volume o0.5 ml/kg/h for 6 hours.
  • Requirement of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [ Time Frame: 30 days ]
  • Cardiac injury [ Time Frame: 30 days ]
    Measured by troponin and NTproBNPlevels
  • Hypercoagulability [ Time Frame: 30 days ]
    measured by D-dimer and fibrinogen levels
  • Disseminated Intravascular Coagulation (DIC) Score [ Time Frame: 30 days ]
    Platelet Count >100 x 109/L 0 Points >50 - <100 x 109/L 1 Point <50 x 109/L 2 Points Increase in Fibrin-related Markers [D Dimers] No change 0 Points Moderate rise 2 Points Strong rise 3 Points Prothrombin Time [PT] Prolongation 3 s or less 0 Points >3 s but <6 s 1 Point >6 s 2 Points Fibrinogen [Clauss] Level >1.0 g/L 0 Points <1.0 g/L 1 Point Score 0-8 Interpretation of Score < 5 Suggestive of non-overt/low grade DIC. Repeat in 1-2 days. ≥ 5 Laboratory evidence consistent with overt DIC.
  • Length of Hospital Stay [ Time Frame: 30 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • Incidence of Renal failure [ Time Frame: 21 days ]
  • Days of hypoxemia [ Time Frame: 21 days ]
    SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support
  • Cardiac injury (e.g. troponin, NTproBNP) [ Time Frame: 21 days ]
  • Hypercoagulability (e.g. D-dimer, fibrinogen) [ Time Frame: 21 days ]
  • DIC score [ Time Frame: 21 days ]
  • Incidence of major bleeding [ Time Frame: 21 days ]
  • Time to change in NEWS2 from baseline [ Time Frame: 30 days ]
  • Requirement of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [ Time Frame: 21 days ]
  • Requirement of non-invasive ventilation or high flow oxygen devices [ Time Frame: 21 days ]
  • Requirement of supplemental oxygen [ Time Frame: 21 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 20, 2020)
  • Length of hospital stay [ Time Frame: 21 days ]
  • Number of days requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [ Time Frame: 21 days ]
  • Number of days requiring non-invasive ventilation or high flow oxygen devices [ Time Frame: 21 days ]
  • Number of days requiring supplemental oxygen [ Time Frame: 21 days ]
 
Descriptive Information
Brief Title  ICMJE A Randomized Trial of Anticoagulation Strategies in COVID-19
Official Title  ICMJE A Randomized Trial of Anticoagulation Strategies in COVID-19
Brief Summary This is a randomized open label trial to compare effectiveness of two dosing regimens currently used for prevention of clotting events in COVID-19 positive inpatients. Both doses and routes of anticoagulation regimens are currently used in COVID-19 positive inpatients at NYU Langone Health.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The proposed study is designed as an open label randomized trial of patients hospitalized COVID-19 positive patients with an elevated D-dimer. Patients will be randomized to higher-dose (e.g. therapeutic) anticoagulation versus lower-dose (e.g. prophylactic) anticoagulation in 1:1 ratio.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Enoxaparin Higher Dose

    Drug: Enoxaparin Higher Dose

    • Enoxaparin in patients with a Cr Clearance of > 30
    • Enoxaparin 1mg/kg q12 SQ hours for weight 50-150kg
    • Enoxaparin 0.75mg/kg q12 SQ hours for weight >150kg or BMI >40
    • Unfractionated IV heparin titrated to a goal antiXa of 0.3-0.5 unit/mL (may be used as an alternative)

    For Enoxaparin, AntiXA testing will be done after fourth injection only for participants with BMI >40 or weight > 150 kg as per institutional policy.

  • Drug: Lower-dose prophylactic anticoagulation

    Drug: Lower-dose prophylactic anticoagulation

    • Heparin 5000 units every 12 or every 8 hours or 7500 units every 8 hours for BMI > 40 or weight > 150 kg, or
    • Enoxaparin 40mg every 24 hours or 30mg every 12 hours or every 24 hours (with CrCl < 30mL/min) SQ or
    • Enoxaparin 40mg every 12 hours SQ for weight >150kg or BMI >40-50
    • Enoxaparin 60 mg every 12 hours SQ for BMI >50

    For Enoxaparin, AntiXA testing will be done after fourth injection only for participants with BMI >40 or weight > 150kg as per institutional policy.

    For patients that develop acute kidney injury, and received enoxaparin, transition to IV unfractionated heparin by checking antiXa when next dose of enoxaparin would be due and initiating IV heparin when antiXa <0.7 IU/mL

Study Arms  ICMJE
  • Experimental: Higher-dose anticoagulation
    Intervention: Drug: Enoxaparin Higher Dose
  • Experimental: Lower-dose prophylactic anticoagulation
    Intervention: Drug: Lower-dose prophylactic anticoagulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2020)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 21, 2021
Estimated Primary Completion Date April 21, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. >18 years of age
  2. Hospitalized patient with a diagnosis of COVID-19
  3. Elevated D-dimer within prior 48 hours. Definition of elevated D-dimer is site-determined

Exclusion Criteria:

  1. Meeting alternative indication for higher-dose anticoagulation

    1. Prevalent blood clot at the time of enrollment
    2. D-dimer >10,000 ng/ml
    3. Rapidly rising D-dimer (change in D-dimer >10X over the prior 48 hours)
    4. Prior VTE
    5. Atrial fibrillation (with a CHADS2 Score >1*)
  2. Renal failure (Creatinine clearance <15 and/or requirement of renal replacement therapies)
  3. Heparin induced thrombocytopenia within 100 days
  4. Stroke within 30 days
  5. Hemorrhagic stroke (ever)
  6. GI bleed within 6 months
  7. Platelet count <100,000
  8. Anemia with a hemoglobin <9mg/dl
  9. Pregnancy
  10. Signs of active bleeding (e.g. a whole blood or PRBC transfusion in the past 30 days)
  11. Other high bleeding risk (I.e. trauma, use of dual antiplatelet therapy)
  12. CHF, Hypertension, Age>75 years, Diabetes, Prior stroke or TIA symptoms
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeffrey Berger, MD 212-263-4004 PROTECT.COVID19@nyulangone.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04359277
Other Study ID Numbers  ICMJE s20-00479
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: jeffrey.berger@nyumc.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
Access Criteria: Requests may be directed to: jeffrey.berger@nyumc.org. To gain access, data requestors will need to sign a data access agreement.
Responsible Party NYU Langone Health
Study Sponsor  ICMJE NYU Langone Health
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Berger, MD NYU Langone Health
PRS Account NYU Langone Health
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP