Pro-thrombotic Status in Patients With SARS-Cov-2 Infection (ATTAC-Co)

Patterns and Changes in Platelet Reactivity, Thrombotic Status and Endothelial Function in Hospitalized Patients With SARS-Cov-2 Infection

The present study is ideated to prospectively investigate in patients with severe acute respiratory syndrome (SARS) due to Coronavirus 19 (SARS-Cov-2) infection and moderate-severe respiratory failure the patterns and changes in platelet reactivity, thrombotic status and endothelial function. The observed patterns and changes will be related with inflammatory status, myocardial injury and outcomes

Study Overview

• Status: Active, not recruiting
• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2
• Intervention / Treatment: Other: SARS-Cov-2 infection

Detailed Description

Preliminary evidences suggested that patients with SARS-Cov-2 infection and concomitant presence of cardiovascular risk factors (i.e. arterial hypertension) and/or cardiovascular history (i.e. prior myocardial infarction) are at poor prognosis. The first reports from China suggested in patients with SARS-Cov-2 infection a heightened inflammatory burden associated with significant changes in coagulative status (i.e. low platelet count, increased D-dimer) and dysfunction of micro-vessels in pulmonary circulation.

No data are available about patterns and changes in platelet reactivity, activation of coagulation factors and endothelial function during SARS-Cov-2 infection.

The present study is ideated to fill this gap. Patients with moderate to severe respiratory failure due to SARS-Cov-2 infection will be enrolled. One blood sample will be obtained from each patient at the early, mid and late stage of disease. Several markers of platelet, coagulation and endothelial function will be related with laboratory, clinical, electrocardiographic, imaging (transthoracic echocardiogram, pulmonary ultrasonography, computed tomography) and outcome data.

To better describe typical patterns of disease regarding inflammation, platelet function and coagulation alteration, data from cases will be compared with control groups negative for SARS-CoV-2 infection, but with ST-segment elevation myocardial infarction or moderate-severe respiratory failure due to other agents.

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Veronica Lodolini; Phone Number: 0532237079; Email: ldlvnc@unife.it

Study Locations

• Italy
  • Ferrara, Italy
    • Azienda Ospedaliera Universitaria di Ferrara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of moderate-severe respiratory failure (PaO2/FiO2 <200)

• Diagnosis of SARS-CoV-2 infection + one of the following

  1. invasive mechanical ventilation (cohort A)
  2. non invasive mechanical ventilation (cohort B)
  3. only oxygen support

Exclusion Criteria:

• Previous chronic use of P2Y12 inhibitors
• Need for chronic oral anti-coagulation therapy
• Know disorder of coagulation or platelet function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: SARS-Cov-2 infection; Single study group of patients with respiratory failure due to SARS-Cov-2 infection. Three blood samples will be collected at different stages of disease: early, defined as first 96 hours, mid, defined as time from 96 hours and 14 days, late. defined as >14 days	Other: SARS-Cov-2 infection; blood sample withdrawal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
on-treatment platelet reactivity	patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli	early stage of disease (first 96 hours)
on-treatment platelet reactivity	patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli	mid stage of disease (96 hours - 14 days)
on-treatment platelet reactivity	patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli	late stage of disease (>14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
apoptosis rate in human umbilical vein endothelial cells (HUVEC)	patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study.	early stage of disease (first 96 hours)
apoptosis rate in human umbilical vein endothelial cells (HUVEC)	patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study.	mid stage of disease (96 hours - 14 days)
Nitric oxide (NO) intracellular levels	patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.	late stage of disease (>14 days)
Nitric oxide (NO) intracellular levels	patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.	early stage of disease (first 96 hours)
Nitric oxide (NO) intracellular levels	patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.	mid stage of disease (96 hours - 14 days)
reactive oxygen species (ROS) levels	patterns and changes of ROS	early stage of disease (first 96 hours)
reactive oxygen species (ROS) levels	patterns and changes of ROS	mid stage of disease (96 hours - 14 days)
reactive oxygen species (ROS) levels	patterns and changes of ROS	late stage of disease (>14 days)
coagulation factors levels	patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)	early stage of disease (first 96 hours)
coagulation factors levels	patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)	mid stage of disease (96 hours - 14 days)
coagulation factors levels	patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)	late stage of disease (>14 days)
respiratory function	values of FEV1% as assessed by spirometry	6-month
respiratory function	values of FEV1% as assessed by spirometry	12-month
cardiac function	values of left ventricular ejection fraction as assessed by transthoracic echocardiogram	6-month
cardiac function	values of left ventricular ejection fraction as assessed by transthoracic echocardiogram	12-month
clinical outcome	occurrence of death, myocardial infarction, stroke and other major adverse events	12-month

Collaborators and Investigators

• Sponsor: University Hospital of Ferrara
• Investigators: Principal Investigator: Savino Spadaro, MD, Intensive care unit; Principal Investigator: Gianluca Campo, MD, Cardiology Unit; Principal Investigator: Marco Contoli, MD, Pulmonology Unit

Publications and helpful links

General Publications

• Scaramuzzo G, Ronzoni L, Campo G, Priani P, Arena C, La Rosa R, Turrini C, Volta CA, Papi A, Spadaro S, Contoli M. Long-term dyspnea, regional ventilation distribution and peripheral lung function in COVID-19 survivors: a 1 year follow up study. BMC Pulm Med. 2022 Nov 9;22(1):408. doi: 10.1186/s12890-022-02214-5.
• Contoli M, Papi A, Tomassetti L, Rizzo P, Vieceli Dalla Sega F, Fortini F, Torsani F, Morandi L, Ronzoni L, Zucchetti O, Pavasini R, Fogagnolo A, Volta CA, Bartlett NW, Johnston SL, Spadaro S, Campo G. Blood Interferon-alpha Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients. Front Immunol. 2021 Mar 9;12:648004. doi: 10.3389/fimmu.2021.648004. eCollection 2021.
• Spadaro S, Fogagnolo A, Campo G, Zucchetti O, Verri M, Ottaviani I, Tunstall T, Grasso S, Scaramuzzo V, Murgolo F, Marangoni E, Vieceli Dalla Sega F, Fortini F, Pavasini R, Rizzo P, Ferrari R, Papi A, Volta CA, Contoli M. Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients. Crit Care. 2021 Feb 19;25(1):74. doi: 10.1186/s13054-021-03499-4.
• Campo G, Contoli M, Fogagnolo A, Vieceli Dalla Sega F, Zucchetti O, Ronzoni L, Verri M, Fortini F, Pavasini R, Morandi L, Biscaglia S, Di Ienno L, D'Aniello E, Manfrini M, Zoppellari R, Rizzo P, Ferrari R, Volta CA, Papi A, Spadaro S. Over time relationship between platelet reactivity, myocardial injury and mortality in patients with SARS-CoV-2-associated respiratory failure. Platelets. 2021 May 19;32(4):560-567. doi: 10.1080/09537104.2020.1852543. Epub 2020 Dec 3.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Actual): November 12, 2023
• Study Completion (Estimated): November 12, 2024

Study Registration Dates

• First Submitted: April 3, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 12, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19
• Other Study ID Numbers: 250320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After specific request to study PIs
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No