Pro-thrombotic Status in Patients With SARS-Cov-2 Infection (ATTAC-Co)
Primary Purpose
Severe Acute Respiratory Syndrome Coronavirus 2
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
SARS-Cov-2 infection
Sponsored by
About this trial
This is an interventional diagnostic trial for Severe Acute Respiratory Syndrome Coronavirus 2
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of moderate-severe respiratory failure (PaO2/FiO2 <200)
Diagnosis of SARS-CoV-2 infection + one of the following
- invasive mechanical ventilation (cohort A)
- non invasive mechanical ventilation (cohort B)
- 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
Sites / Locations
- Azienda Ospedaliera Universitaria di FerraraRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
SARS-Cov-2 infection
Arm Description
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
Outcomes
Primary Outcome Measures
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
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
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
Secondary Outcome Measures
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.
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.
Nitric oxide (NO) intracellular levels
patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Nitric oxide (NO) intracellular levels
patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Nitric oxide (NO) intracellular levels
patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
reactive oxygen species (ROS) levels
patterns and changes of ROS
reactive oxygen species (ROS) levels
patterns and changes of ROS
reactive oxygen species (ROS) levels
patterns and changes of ROS
coagulation factors levels
patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
coagulation factors levels
patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
coagulation factors levels
patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
respiratory function
values of FEV1% as assessed by spirometry
respiratory function
values of FEV1% as assessed by spirometry
cardiac function
values of left ventricular ejection fraction as assessed by transthoracic echocardiogram
cardiac function
values of left ventricular ejection fraction as assessed by transthoracic echocardiogram
clinical outcome
occurrence of death, myocardial infarction, stroke and other major adverse events
Full Information
NCT ID
NCT04343053
First Posted
April 3, 2020
Last Updated
November 1, 2022
Sponsor
University Hospital of Ferrara
1. Study Identification
Unique Protocol Identification Number
NCT04343053
Brief Title
Pro-thrombotic Status in Patients With SARS-Cov-2 Infection
Acronym
ATTAC-Co
Official Title
Patterns and Changes in Platelet Reactivity, Thrombotic Status and Endothelial Function in Hospitalized Patients With SARS-Cov-2 Infection
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 8, 2020 (Actual)
Primary Completion Date
June 9, 2023 (Anticipated)
Study Completion Date
June 9, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital of Ferrara
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Acute Respiratory Syndrome Coronavirus 2
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Technicians performing assays will be blinded to stage of the infection and outcomes
Allocation
N/A
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SARS-Cov-2 infection
Arm Type
Other
Arm Description
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
Intervention Type
Other
Intervention Name(s)
SARS-Cov-2 infection
Intervention Description
blood sample withdrawal
Primary Outcome Measure Information:
Title
on-treatment platelet reactivity
Description
patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli
Time Frame
early stage of disease (first 96 hours)
Title
on-treatment platelet reactivity
Description
patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli
Time Frame
mid stage of disease (96 hours - 14 days)
Title
on-treatment platelet reactivity
Description
patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli
Time Frame
late stage of disease (>14 days)
Secondary Outcome Measure Information:
Title
apoptosis rate in human umbilical vein endothelial cells (HUVEC)
Description
patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study.
Time Frame
early stage of disease (first 96 hours)
Title
apoptosis rate in human umbilical vein endothelial cells (HUVEC)
Description
patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study.
Time Frame
mid stage of disease (96 hours - 14 days)
Title
Nitric oxide (NO) intracellular levels
Description
patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Time Frame
late stage of disease (>14 days)
Title
Nitric oxide (NO) intracellular levels
Description
patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Time Frame
early stage of disease (first 96 hours)
Title
Nitric oxide (NO) intracellular levels
Description
patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Time Frame
mid stage of disease (96 hours - 14 days)
Title
reactive oxygen species (ROS) levels
Description
patterns and changes of ROS
Time Frame
early stage of disease (first 96 hours)
Title
reactive oxygen species (ROS) levels
Description
patterns and changes of ROS
Time Frame
mid stage of disease (96 hours - 14 days)
Title
reactive oxygen species (ROS) levels
Description
patterns and changes of ROS
Time Frame
late stage of disease (>14 days)
Title
coagulation factors levels
Description
patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
Time Frame
early stage of disease (first 96 hours)
Title
coagulation factors levels
Description
patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
Time Frame
mid stage of disease (96 hours - 14 days)
Title
coagulation factors levels
Description
patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
Time Frame
late stage of disease (>14 days)
Title
respiratory function
Description
values of FEV1% as assessed by spirometry
Time Frame
6-month
Title
respiratory function
Description
values of FEV1% as assessed by spirometry
Time Frame
12-month
Title
cardiac function
Description
values of left ventricular ejection fraction as assessed by transthoracic echocardiogram
Time Frame
6-month
Title
cardiac function
Description
values of left ventricular ejection fraction as assessed by transthoracic echocardiogram
Time Frame
12-month
Title
clinical outcome
Description
occurrence of death, myocardial infarction, stroke and other major adverse events
Time Frame
12-month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of moderate-severe respiratory failure (PaO2/FiO2 <200)
Diagnosis of SARS-CoV-2 infection + one of the following
invasive mechanical ventilation (cohort A)
non invasive mechanical ventilation (cohort B)
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Veronica Lodolini
Phone
0532237079
Email
ldlvnc@unife.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Savino Spadaro, MD
Organizational Affiliation
Intensive care unit
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gianluca Campo, MD
Organizational Affiliation
Cardiology Unit
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marco Contoli, MD
Organizational Affiliation
Pulmonology Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
Azienda Ospedaliera Universitaria di Ferrara
City
Ferrara
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Veronica Lodolini
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
After specific request to study PIs
Citations:
PubMed Identifier
36352423
Citation
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.
Results Reference
derived
PubMed Identifier
33767713
Citation
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.
Results Reference
derived
PubMed Identifier
33608030
Citation
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.
Results Reference
derived
PubMed Identifier
33270471
Citation
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.
Results Reference
derived
Learn more about this trial
Pro-thrombotic Status in Patients With SARS-Cov-2 Infection
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