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

COVID-19 Clinical Trial

— IMPACT  

Official title:

InterMediate ProphylACtic Versus Therapeutic Dose Anticoagulation in Critically Ill Patients With COVID-19: A Prospective Randomized Study (The IMPACT Trial)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04406389
• Other study ID #: 20-04021936
• Status: Terminated
• Phase: Phase 4
• Start date: October 13, 2020
• Est. completion date: April 21, 2022

Study information

• Verified date: August 2023
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: April 21, 2022
• Est. primary completion date: April 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• 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
• 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
• 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
• Argatroban
Therapeutic Dose Anticoagulation Arm: Dosed according to institutional protocol

Locations

Country	Name	City	State
United States	New York Presbyterian Brooklyn Methodist Hospital	Brooklyn	New York
United States	Weill Cornell Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30-day Mortality	Comparison of number of COVID-19 positive patients who have died within 30 days of starting treatment on each treatment arm	30 days
Secondary	Length of Intensive Care Unit (ICU) Stay in Days	Comparison of length of ICU stay in days between each treatment arm.	6 months
Secondary	Number of Documented Venous Thromboembolism (VTE), Arterial Thrombosis (Stroke, Myocardial Infarction, Other) and Microthrombosis Events	Comparison of number of documented VTE, arterial thrombosis and microthrombosis events on each treatment arm	6 months
Secondary	Number of Major and Clinically Relevant Non-major Bleeding Events	Comparison of major and clinically-relevant non-major bleeding events on each treatment arm, as defined by the International Society of Thrombosis and Haemostasis (ISTH) criteria.	6 months