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

NCT ID: NCT04406389

Last Updated: 2023-09-21

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-13

Study Completion Date

2022-04-21

Brief Summary

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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.

Detailed Description

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Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Enoxaparin sodium

Intervention Type 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

Unfractionated heparin

Intervention Type DRUG

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

Intervention Type DRUG

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

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:

* ≥100 kg: 10 mg daily
* \<100 kg but ≥50 kg: 7.5 mg daily
* \<50 kg: 5 mg daily

Group Type EXPERIMENTAL

Enoxaparin sodium

Intervention Type 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

Unfractionated heparin

Intervention Type DRUG

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

Intervention Type DRUG

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

Argatroban

Intervention Type DRUG

Therapeutic Dose Anticoagulation Arm:

Dosed according to institutional protocol

Interventions

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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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

Argatroban

Therapeutic Dose Anticoagulation Arm:

Dosed according to institutional protocol

Intervention Type DRUG

Other Intervention Names

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Lovenox Sodium heparin Arixtra

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Weill Medical College of Cornell University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maria T DeSancho, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

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New York Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 32073213 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32220112 (View on PubMed)

Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020 May 14;41(19):1798-1800. doi: 10.1093/eurheartj/ehaa231. No abstract available.

Reference Type BACKGROUND
PMID: 32186331 (View on PubMed)

Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res. 2008;122(6):743-52. doi: 10.1016/j.thromres.2006.10.026. Epub 2007 Aug 28.

Reference Type BACKGROUND
PMID: 17727922 (View on PubMed)

Esmon CT. Targeting factor Xa and thrombin: impact on coagulation and beyond. Thromb Haemost. 2014 Apr 1;111(4):625-33. doi: 10.1160/TH13-09-0730. Epub 2013 Dec 12.

Reference Type BACKGROUND
PMID: 24336942 (View on PubMed)

Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017 Feb 28;117(3):437-444. doi: 10.1160/TH16-08-0620. Epub 2016 Dec 15.

Reference Type BACKGROUND
PMID: 27975101 (View on PubMed)

Hanify JM, Dupree LH, Johnson DW, Ferreira JA. Failure of chemical thromboprophylaxis in critically ill medical and surgical patients with sepsis. J Crit Care. 2017 Feb;37:206-210. doi: 10.1016/j.jcrc.2016.10.002. Epub 2016 Oct 11.

Reference Type BACKGROUND
PMID: 27969572 (View on PubMed)

Thachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020 May;18(5):1020-1022. doi: 10.1111/jth.14821. Epub 2020 Apr 27. No abstract available.

Reference Type BACKGROUND
PMID: 32239799 (View on PubMed)

Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020 Jun;18(6):1421-1424. doi: 10.1111/jth.14830. Epub 2020 May 6.

Reference Type BACKGROUND
PMID: 32271988 (View on PubMed)

Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10.

Reference Type BACKGROUND
PMID: 32291094 (View on PubMed)

Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.

Reference Type BACKGROUND
PMID: 15842354 (View on PubMed)

Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, Merdji H, Clere-Jehl R, Schenck M, Fagot Gandet F, Fafi-Kremer S, Castelain V, Schneider F, Grunebaum L, Angles-Cano E, Sattler L, Mertes PM, Meziani F; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020 Jun;46(6):1089-1098. doi: 10.1007/s00134-020-06062-x. Epub 2020 May 4.

Reference Type BACKGROUND
PMID: 32367170 (View on PubMed)

Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Muller MCA, Bouman CCS, Beenen LFM, Kootte RS, Heijmans J, Smits LP, Bonta PI, van Es N. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020 Aug;18(8):1995-2002. doi: 10.1111/jth.14888. Epub 2020 Jul 27.

Reference Type BACKGROUND
PMID: 32369666 (View on PubMed)

Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, Satlin MJ, Campion TR Jr, Nahid M, Ringel JB, Hoffman KL, Alshak MN, Li HA, Wehmeyer GT, Rajan M, Reshetnyak E, Hupert N, Horn EM, Martinez FJ, Gulick RM, Safford MM. Clinical Characteristics of Covid-19 in New York City. N Engl J Med. 2020 Jun 11;382(24):2372-2374. doi: 10.1056/NEJMc2010419. Epub 2020 Apr 17. No abstract available.

Reference Type BACKGROUND
PMID: 32302078 (View on PubMed)

Paranjpe I, Fuster V, Lala A, Russak AJ, Glicksberg BS, Levin MA, Charney AW, Narula J, Fayad ZA, Bagiella E, Zhao S, Nadkarni GN. Association of Treatment Dose Anticoagulation With In-Hospital Survival Among Hospitalized Patients With COVID-19. J Am Coll Cardiol. 2020 Jul 7;76(1):122-124. doi: 10.1016/j.jacc.2020.05.001. Epub 2020 May 6. No abstract available.

Reference Type BACKGROUND
PMID: 32387623 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35244208 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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20-04021936

Identifier Type: -

Identifier Source: org_study_id

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