Anticoagulation in Critically Ill Patients With COVID-19 (The IMPACT Trial)

Weill Cornell Medicine (WCM)

Status and phase: Terminated; Phase 4

Conditions: COVID-19

Treatments: Drug: Enoxaparin sodium; Drug: Unfractionated heparin; Drug: Fondapariniux; Drug: Argatroban

Study type: Interventional

Funder types: Other

Identifiers

NCT04406389

20-04021936

Details and patient eligibility

About

The purpose of this study is to determine if therapeutic dose anticoagulation (experimental group) improves 30-day mortality in participants with COVID-19 compared to those patients receiving the intermediate dose prophylaxis (control group). Following screening, subjects will be randomized 1:1 to intermediate dose prophylaxis or therapeutic dose anticoagulation treatment arms.Treatment will continue for 28 days, followed by a 6 month follow-up period.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age >18 years old
• COVID-19 positive on (RT-PCR) nasopharyngeal swab, or suspected COVID-19 infection with detectable SARS-CoV-2 IgG or IgM.
• Intensive care unit (ICU) patient or non-ICU patient on invasive mechanical ventilation, BiPAP, 100% non-rebreather mask, or high flow oxygen or supplemental oxygen of at least 4 liters per minute nasal cannula.
• D dimer level greater than 700 ng/mL (3 times the upper limit of normal).

Exclusion criteria

• Objectively documented deep vein thrombosis or pulmonary embolism
• Patients in whom there is very high suspicion for pulmonary embolism and are on full-dose anticoagulation as per the treating physician
• Platelets <30,000 not due to disseminated intravascular coagulation (DIC), based on the International Society of Thrombosis and Haemostasis (ISTH) criteria and American Society of Hematology (ASH) Frequently Asked Questions
• Active bleeding that poses a contraindication to therapeutic anticoagulation in the opinion of the investigator.
• History of bleeding diathesis (e.g., hemophilia, severe von Willebrand disease, severe thrombocytopathy)
• History of intracranial hemorrhage in the last 90 days
• History of ischemic stroke in the past 2 weeks
• Major neurosurgical procedure in the past 30 days
• Cardiothoracic surgery in the past 30 days
• Intra-abdominal surgery in the past 30 days
• Intracranial malignancy
• Patients who require therapeutic anticoagulation for other reasons like atrial fibrillation, deep venous thrombosis, pulmonary embolism, or antiphospholipid syndrome.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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14 participants in 2 patient groups

Intermediate Dose Prophylaxis

Active Comparator group

Description:

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

Treatment:

Drug: Fondapariniux

Drug: Unfractionated heparin

Drug: Enoxaparin sodium

Therapeutic Dose Anticoagulation

Experimental group

Description:

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

Treatment:

Drug: Fondapariniux

Drug: Argatroban

Drug: Unfractionated heparin

Drug: Enoxaparin sodium