Intermediate or Prophylactic-Dose Anticoagulation for Venous or Arterial Thromboembolism in Severe COVID-19

NCT04367831 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: AAAS8980
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to assess the effectiveness of intermediate versus prophylactic doses of anticoagulation (blood thinners) in patients critically ill with COVID-19 in the intensive care units (ICUs) throughout the hospital. Anticoagulation is part of the patient's usual standard of care but determining the dose of anticoagulation is based on physician preference. The investigators are conducting this study (a randomized trial with adaptive design employing cluster randomization) with the support of all of the ICUs to collect data in order to determine what should be the standard of care in terms of anticoagulation in these critically ill patients. The patients care will not be altered other than the choice of anticoagulation (both approved and used throughout the hospital as standard of care) based on the ICU bed they are assigned. Patient data will be collected until discharge.

Conditions

COVID-19; Venous Thromboses; Arterial Thrombosis

Keywords

COVID-19; coronavirus; anticoagulation

Outcome Measures

Primary Outcomes (1)

• Total Number of Patients Who Were Alive and Without Venous/Thrombotic Events in ICU

  Composite of being alive and without clinically-relevant venous or arterial thrombotic events at discharge from ICU (without transfer to another ICU or palliative care unit/hospice) or at 30 days (if ICU duration lasted 30 days or longer).

  Discharge from ICU or 30 days

Secondary Outcomes (5)

• Total Number of Patients With Clinically Relevant Venous or Arterial Thrombotic Events in ICU

  Discharge from hospital or 30 days

• ICU Length of Stay

  Discharge from ICU, up to 36 days

• Total Number of Patients With the Need for Renal Replacement Therapy in the ICU

  Discharge from ICU or 30 days

• Total Number of Patients With Major Bleeding in the ICU

  Discharge from ICU or 30 days

• Hospital Length of Stay

  Discharge from ICU, up to 36 days

Study Arms (2)

Intervention arm: intermediate-dose anticoagulation

EXPERIMENTAL

If estimated glomerular filtration rate (eGFR) ≥ 30 mL/min: enoxaparin 1mg/kg subcutaneous (SC) daily or unfractionated heparin infusion at 10 units/kg/hour with goal anti-Xa 0.1-0.3 U/mL. If eGFR \<30 mL/min or acute kidney injury or CRRT: Unfractionated heparin infusion at 10 units/kg/hour (minimum 500 units/hour if CRRT) with goal anti-Xa 0.1-0.3 U/mL

Drug: Heparin Infusion; Drug: Enoxaparin/Lovenox Intermediate Dose

Control arm: prophylaxis

ACTIVE COMPARATOR

Prophylactic dose anticoagulation (per Columbia University Irving Medical Center (CUIMC) Guidelines): If eGFR ≥30 mL/min (stable kidney function): 1. BMI \< 40 kg/m2: Enoxaparin 40 mg SC daily 2. BMI 40 - 50 kg/m2: Enoxaparin 40 mg SC q12h 3. BMI \> 50 kg/m2: Enoxaparin 60 mg SC q12h If eGFR \< 30 mL/min or acute kidney injury: 1. 50-120 kg: Unfractionated heparin 5000 units SC q8h 2. \>120 kg: Unfractionated heparin 7500 units SC q8h If CRRT: Unfractionated heparin infusion pre-filter at 500 units/hour

Drug: Enoxaparin Prophylactic Dose; Drug: Heparin SC

Interventions

Enoxaparin Prophylactic Dose DRUG

Prophylactic dose anticoagulation (per Columbia University Irving Medical Center (CUIMC) Guidelines): If eGFR ≥30 mL/min (stable kidney function): 1. BMI \< 40 kg/m2: Enoxaparin 40 mg SC daily 2. BMI 40 - 50 kg/m2: Enoxaparin 40 mg SC q12h 3. BMI \> 50 kg/m2: Enoxaparin 60 mg SC q12h

Also known as: Lovenox

Control arm: prophylaxis

Heparin Infusion DRUG

Unfractionated heparin infusion at 10 units/kg/hour with goal anti-Xa 0.1 -0.3U/mL.

Also known as: Heparin

Intervention arm: intermediate-dose anticoagulation

Heparin SC DRUG

Unfractionated heparin at 5000-7500 units subcutaneous (SC) every 8 hours.

Also known as: Heparin

Control arm: prophylaxis

Enoxaparin/Lovenox Intermediate Dose DRUG

If estimated glomerular filtration rate (eGFR) ≥ 30 mL/min: enoxaparin 1mg/kg subcutaneous (SC) daily.

Also known as: Lovenox

Intervention arm: intermediate-dose anticoagulation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR)
• New admission to eligible CUIMC ICUs within 5 days
• Transfer from nonparticipating to participating ICU is eligible if otherwise meets eligibility criteria.
• Patients transferred between participating ICUs will maintain initial treatment assignment.
• Patients not on therapeutic anticoagulation and who were already admitted to participating ICU within 5 days of trial initiation are additionally eligible.

You may not qualify if:

• Weight under 50kg
• Contraindication to anticoagulation in the opinion of the treating clinician including
• overt bleeding
• platelet count \<50,000
• Bleeding Academic Research Consortium (BARC) major bleeding in the past 30 days
• Gastrointestinal (GI) bleeding within 3 months
• history of intracranial hemorrhage
• Ischemic stroke within the past 2 weeks
• craniotomy/major neurosurgery within the past 30 days
• cardiothoracic surgery within the past 30 days
• intra-abdominal surgery within 30 days prior to enrollment
• Head or spinal trauma in the last months
• History of uncorrected cerebral aneurysm or arteriovenous malformation (AVM)
• Intracranial malignancy
• Presence of an epidural or spinal catheter

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (3)

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

  PMID: 35244208 DERIVED

• Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.

  PMID: 33502773 DERIVED

• Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020 Jun;7(6):e438-e440. doi: 10.1016/S2352-3026(20)30145-9. Epub 2020 May 11. No abstract available.

  PMID: 32407672 DERIVED

MeSH Terms

Conditions

COVID-19; Venous Thrombosis; Coronavirus Infections

Interventions

Enoxaparin; Heparin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Sahil A. Parikh, MD
• Organization: Columbia University

sap2196@cumc.columbia.edu

212-305-3617

Study Officials

• Ajay Kirtane, MD

  Columbia University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 29, 2020
• Study Start: May 2, 2020
• Primary Completion: May 12, 2021
• Study Completion: May 12, 2021
• Last Updated: December 10, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)