Pro-thrombotic Status in Patients with SARS-Cov-2 Infection

Not Applicable

Completed

• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2
• Interventions: Other: SARS-Cov-2 infection

• Registration Number: NCT04343053
• Lead Sponsor: University Hospital of Ferrara

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.

Study Timeline

• Study First Submitted: 2020-04-03
• Study Start: 2020-04-08
• Study First Submitted QC: 2020-04-08
• Study First Posted: 2020-04-13
• Primary Completion: 2023-11-12
• Status Verified: 2024-12
• Study Completion: 2024-12-07
• Last Update Submitted: 2024-12-07
• Last Update Posted: 2024-12-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 145

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SARS-Cov-2 infection	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

Primary Outcome Measures

Name	Time	Method
on-treatment platelet reactivity	late stage of disease (>14 days)	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

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

Trial Locations

Locations (1)

Azienda Ospedaliera Universitaria di Ferrara; 🇮🇹 Ferrara, Italy