Clinical trial NCT04343053: Pro-thrombotic Status in Patients with SARS-Cov-2 Infection
Official title: Patterns and Changes in Platelet Reactivity, Thrombotic Status and Endothelial Function in Hospitalized Patients with SARS-Cov-2 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Acute Respiratory Syndrome Coronavirus 2
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
First posted: 2020-04-13
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: on-treatment platelet reactivity
timeFrame: early stage of disease (first 96 hours)
measure: on-treatment platelet reactivity
timeFrame: mid stage of disease (96 hours - 14 days)
measure: on-treatment platelet reactivity
timeFrame: late stage of disease (>14 days)
Secondary outcomes:
measure: apoptosis rate in human umbilical vein endothelial cells (HUVEC)
timeFrame: early stage of disease (first 96 hours)
measure: apoptosis rate in human umbilical vein endothelial cells (HUVEC)
timeFrame: mid stage of disease (96 hours - 14 days)
measure: Nitric oxide (NO) intracellular levels
timeFrame: late stage of disease (>14 days)
measure: Nitric oxide (NO) intracellular levels
timeFrame: early stage of disease (first 96 hours)
measure: Nitric oxide (NO) intracellular levels
timeFrame: mid stage of disease (96 hours - 14 days)
measure: reactive oxygen species (ROS) levels
timeFrame: early stage of disease (first 96 hours)
measure: reactive oxygen species (ROS) levels
timeFrame: mid stage of disease (96 hours - 14 days)
measure: reactive oxygen species (ROS) levels
timeFrame: late stage of disease (>14 days)
measure: coagulation factors levels
timeFrame: early stage of disease (first 96 hours)
measure: coagulation factors levels
timeFrame: mid stage of disease (96 hours - 14 days)
measure: coagulation factors levels
timeFrame: late stage of disease (>14 days)
measure: respiratory function
timeFrame: 6-month
measure: respiratory function
timeFrame: 12-month
measure: cardiac function
timeFrame: 6-month
measure: cardiac function
timeFrame: 12-month
measure: clinical outcome
timeFrame: 12-month
Other outcomes:
Locations:
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria di Ferrara
Study officials:
affiliation: Intensive care unit
name: Savino Spadaro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardiology Unit
name: Gianluca Campo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pulmonology Unit
name: Marco Contoli, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.