COVID-19 Coagulopathy Extension Study

NCT05334615 | Recruiting

• 2 other identifiers: 202112148R01AI162778
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

At the University of Iowa, the investigators led a multicenter randomized clinical trial comparing standard prophylactic dose to intermediate dose enoxaparin in hospitalized patients with COVID-19 (NCT04360824). As part of an exploratory biomarker component of this trial, blood samples were collected from hospitalized COVID-19 patients at enrollment and weekly for up to 30 days of hospitalization. The pilot results, as well as reports from other groups, demonstrate increased potential for thrombin generation in the plasma of COVID-19 patients. In particular, in the COVID-19 patient cohort enhanced thrombin generation potential persisted for at least 30 days of hospitalization. The investigators now propose to explore the mechanistic roles of activation of blood cells (such as platelets and neutrophils) and products of cellular activation as mediators of enhanced thrombin generation in patients with COVID-19. The study design will be a longitudinal cohort study, which will allow for the determination of the time course of enhanced thrombin generation potential in relation to clinical outcomes and changes in markers of cellular activation in serial samples obtained from COVID-19 patients for up to 3 years after infection with SARS-CoV-2. This study may provide clues to why a subset of COVID-19 patients present with late thrombotic complications even after apparent recovery from SARS-CoV-2 infection. An ongoing question in the field relates to the comparative prothrombotic effects of acute COVID-19 versus incidental SARS-CoV-2 infection versus acute infection with influenza viruses. Therefore, we will include three categories of hospitalized patients in this study: (1) acute COVID-19, (2) incidental COVID-19, and (3) acute influenza A or B. This project has a strong scientific rationale with direct clinical implications, especially given the emergence of SARS-CoV-2 variants such as delta and omicron that may prolong the pandemic and/or cause surges of COVID-19 in the coming months.

Conditions

COVID-19

Keywords

thrombosis; coagulopathy; influenza

Outcome Measures

Primary Outcomes (3)

• Thrombin generation

  Determine the time course of enhanced thrombin generation potential in patients with COVID-19 or influenza

  3 years

• Blood cell activation

  Test the hypothesis that activation of platelets, neutrophils, and endothelial cells by plasma from COVID-19 patients is mediated by Gal-3, IL6, and/or histones.

  3 years

• Cellular mediators of thrombin generation

  Determine the roles of neutrophils, platelets and endothelial cells in mediating increased thrombin generation and whether targeting IL6, Gal-3, or histones decreases thrombin generation potential in plasma samples from COVID-19 patients.

  3 years

Secondary Outcomes (2)

• Biomarkers

  3 years

• Association of biomarkers with thrombin generation

  3 years

Study Arms (3)

Acute COVID-19

Hospital admission for management of symptoms related to COVID-19. Laboratory confirmed infection with SARS-CoV-2 by either PCR or antigen testing within 4 weeks of hospital admission. Age ≥18 years.

Incidental COVID-19

Hospital admission for indications unrelated to COVID-19 who are incidentally found to have infection with SARS-CoV-2. Age ≥18 years.

Acute influenza

Hospital admission for clinical management of symptoms related to influenza. Laboratory confirmed infection with influenza A or influenza B within 4 weeks of hospital admission. Negative testing for SARS-CoV-2. Age ≥18 years.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Hospitalized patients with acute COVID-19 (laboratory-confirmed SARS-CoV-2 infection) Hospitalized patients with incidental COVID-19 (laboratory-confirmed SARS-CoV-2 infection) Hospitalized patients with acute influenza (laboratory confirmed infection with influenza A or influenza B)

You may qualify if:

• Acute COVID-19
• Hospital admission for management of symptoms related to COVID-19
• Laboratory confirmed infection with SARS-CoV-2 by either PCR or antigen testing within 4 weeks of hospital admission
• Age ≥18 years
• Incidental COVID-19
• Hospital admission for indications unrelated to COVID-19 who are incidentally found to have infection with SARS-CoV-2
• Age ≥18 years
• Acute influenza
• Hospital admission for clinical management of symptoms related to influenza
• Laboratory confirmed infection with influenza A or influenza B within 4 weeks of hospital admission
• Negative testing for SARS-CoV-2
• Age ≥18 years

You may not qualify if:

• Current pregnancy
• Prisoner
• History of a bleeding disorder
• Active cancer

Sponsors & Collaborators

• University of Iowa: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

RECRUITING

Related Publications (1)

• Perepu US, Chambers I, Wahab A, Ten Eyck P, Wu C, Dayal S, Sutamtewagul G, Bailey SR, Rosenstein LJ, Lentz SR. Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial. J Thromb Haemost. 2021 Sep;19(9):2225-2234. doi: 10.1111/jth.15450. Epub 2021 Jul 18.

  PMID: 34236768 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be collected at baseline (within 24 hours of enrollment), weekly thereafter during up to 30 days of hospitalization. After discharge from the hospital, one follow-up visit will occur in 3-6 months. Annual telephone follow-up and optional follow-up visits for blood sample collection will occur at 12, 24, and 36 months after enrollment (+/- 60 days) for a period of 3 years from enrollment.

MeSH Terms

Conditions

COVID-19; Thrombosis; Hemostatic Disorders; Influenza, Human

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Orthomyxoviridae Infections

Central Study Contacts

Steven Lentz, MD, PhD

CONTACT

+1 319 356 4048; steven-lentz@uiowa.edu

Gokul Patil, PhD

CONTACT

+1 319 936 3211; gokul-patil@uiowa.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 17, 2022
• First Posted: April 19, 2022
• Study Start: January 21, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-04

Locations

US (1)