A Phase 3 interventional study of Prasugrel Hydrochloride 10 MG Oral Tablet and Placebo in COVID19 and Thrombosis, sponsored by Azienda Ospedaliera Universitaria Integrata Verona. Status unknown at 1 site in Italy. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2020-06-26.
Sponsored by Azienda Ospedaliera Universitaria Integrata Verona · Phase 3, Interventional, and Treatment
Inflammatory diseases favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended if concomitant inflammatory disease. In severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pneumonia an inflammation-dependent thrombotic process occurs and platelet activation may promote thrombosis and amplify inflammation, as indicated by previous experimental evidence , and the similarities with atherothrombosis and thrombotic microangiopathies. Antiplatelet agents represent the cornerstone in the prevention and treatment of atherosclerotic arterial thromboembolism, with limited efficacy in the context of venous thromboembolism. The use of purinergic receptor P2Y12 inhibitors in pneumococcal pneumonia may improve inflammation and respiratory function in humans. There are no validated protocols for thrombosis prevention in Covid-19. There is scientific rationale to consider a P2Y12 inhibitor for the prevention of thrombosis in the pulmonary circulation and attenuation of inflammation. This is supported by numerous demonstrations of the anti-inflammatory activity of P2Y12 inhibitors and the evidence of improvement in respiratory function both in human and experimental pathology. Prasugrel could be considered as an ideal candidate drug for Covid-19 patients because of higher efficacy and limited Interactions with drugs used in the treatment of Sars-CoV2. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs through an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients could reduce the incidence of pulmonary thrombosis and respiratory and multi-organ failure improving clinical outcome in patients with SARS-CoV2 pneumonia. The prevention of thrombogenic platelet activity with a P2Y12 inhibitor could be superior to fixed dose enoxaparin alone. The proposed treatment is feasible in all coronavirus disease 2019 (COVID-19) patients, regardless of the treatment regimen (antivirals, anti-inflammatory drugs, antibiotics), except for specific contraindications.
Severe respiratory failure and multi-organ damage in coronavirus disease 2019 (COVID-19) patients have not a unitary pathophysiological interpretation. There is evidence of an association between the clinical entity of the disease and its severity with the plasma levels of D-dimer and inflammatory indexes. On the basis of retrospective investigations there is accumulating evidence of alterations in the haemostatic parameters that with increased D-dimer values, increased coagulation time and platelets may be predictors of worse prognosis. A systematic survey conducted in the coronavirus disease 2019 (COVID-19) Centre of the AOUI Verona, as part of the Database and Study on the role of platelets in the clinical manifestations of COVID-19 (Ethics Committee CESC Verona and Rovigo approved) revealed by means of computerized tomography (CT) angiograph in patients with a persistent respiratory deficit and very high D-dimer values mainly multiple, bilateral vascular occlusions involving the segmental and subsegmental branches of the pulmonary arteries. This finding is suggestive of a frequent and clinically relevant thrombotic process in a appreciable number (approximately 20%) of patients with COVID-19 pneumonia hospitalized in medical wards. It is a well-established clinical notion that acute and chronic inflammatory diseases may favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended for medical patient with concomitant neoplasia or inflammatory disease. It is conceivable that under conditions, such as SARS-CoV2 pneumonia, an inflammation-dependent thrombotic process takes place and that platelet activation may play a pathogenic role both in the thrombotic process and in the amplification of the inflammatory process. In fact, there is experimental evidence that platelet activation in inflammation would lead to accelerated coagulation and a thrombotic vascular occlusion, with similarities to what is widely documented in atherothrombosis and thrombotic microangiopathies. The administration of antiplatelet drugs represents the cornerstone for the prevention and treatment of arterial thromboembolism in atherosclerotic disease and has also shown some limited efficacy also in the context of venous and arterial thromboembolism associated with atrial fibrillation. Preliminary observations indicate that the use of purinergic receptor P2Y12 inhibitors during pneumococcal pneumonia may improve the inflammatory process and respiratory function in humans. There are currently no validated protocols for thrombosis prevention in the field of pulmonary viral diseases, in particular COVID-19. There is adequate scientific rationale to consider the use of a P2Y12 inhibitor antiplatelet drug for the prevention of thrombosis in the pulmonary circulation and the attenuation of pulmonary inflammation. The use of a P2Y12 inhibitor is motivated by numerous experimental demonstrations of the anti-inflammatory activity of P2Y12 inhibitors and by the evidence of improvement of respiratory function parameters both in humans and experimental models. Prasugrel could be considered as an ideal candidate drug for administration in Covid-19 patients because of its higher efficacy in acute coronary syndrome compared to clopidogrel. Interactions of prasugrel with drugs used for the treatment of SARS-CoV2 are limited. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs via an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients, like those admitted to medical wards, could reduce the incidence of pulmonary thrombosis as well as respiratory and multi-organ failure, contributing to improve clinical outcome of the patients with pneumonia caused by SARS-CoV2 viruses. The anticoagulant activity exerted by a fixed dose of enoxaparin (4000U/day), recommended in patients with the clinical features described, according to a note of the "Italian Medicines Agency" (AIFA), together with the prevention of thrombogenic activity of platelets by means of a P2Y12 inhibitor could prevent aggravation of COVID-19 patients to a greater extent than enoxaparin alone given at the same dose. Early initiation of treatment should mitigate the presentation of pneumonia. The proposed treatment is feasible in all COVID-19 patients, regardless of the treatment regimen used for their condition (antivirals, anti-inflammatory drugs, antibiotics), except for specific contraindications to the use of prasugrel, or placebo if patients are treated with antiplatelet drugs.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's planned enrollment of 128 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Azienda Ospedaliera Universitaria Integrata Verona is the lead sponsor of 92 studies on the registry; 18 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
film-coated tablets of prasugrel hydrochloride (10 mg daily dose after loading dose of 60 mg)
Drug: Prasugrel Hydrochloride 10 MG Oral Tablet
film-coated tablets of placebo (10 mg daily dose after loading dose of 60 mg)
Drug: Placebo
administration of prasugrel daily for 15 days
administration of placebo daily for 15 days
P/F ratio at day 7
PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected after 7 days of treatment
Time frame: day 7
Daily P/F ratio
PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected daily for 15 days
Time frame: 15 days
Daily need for oxygen supply
daily need for oxygen supply for 15 days
Time frame: 15 days
Need for ICU
Number of patients requiring transfer to the intensive care unit (ICU) by treatment arm
Time frame: day 15 and day 30
Death
death by day 15 and day 30 by treatment arm
Time frame: 15 day and day 30
MOF
Multi-organ failure (MOF) by day 15 and day 30 assessed using sequential organ failure assessment score (SOFA) score (Units 0-4 better outcome, over 30 worse outcome) by treatment arm
Time frame: day 15 and day 30
Discharge
Number of patients discharged after improvement by day 15 and day 30 by treatment arm
Time frame: day 15 and day 30
Clinical progression of the disease SOFA score
Clinical progression of the disease evaluated by SOFA score (Units 0-6 better outcome, 15-24 worse outcome) by day 15 and day 30
Time frame: day 15 and day 30
Clinical progression of the disease APACHE II
Clinical progression of the disease evaluated by Acute Physiology And Chronic Health Evaluation (APACHE II) score (Units 1-5 better outcome, over 30 worse outcome) by day 15 and day 30
Time frame: day 15 and day 30
Venous thrombosis/ pulmonary embolism/thrombosis
Number of patients with venous thrombosis/ pulmonary embolism/thrombosis by day 15 and day 30
Time frame: day 15 and day 30
Need for CT imaging
Number of patients requiring computerized tomography (CT) imaging due to worsening of respiratory function by treatment arm
Time frame: day 15
Daily Temperature
Body temperature measured twice daily for 15 days, C°
Time frame: 15 days
Daily blood pressure
Blood pressure measured twice daily for 15 days, mmHg
Time frame: 15 days
Daily total blood count Hemoglobin
Total blood count measured in venous blood for 15 days, Hemoglobin, g/L (cell/mcL
Time frame: 15 days
Daily total blood count Red Blood Cells
Total blood count measured in venous blood for 15 days, Red Blood cells (cell/mcL)
Time frame: 15 days
Daily total blood count Leukocytes
Total blood count measured in venous blood for 15 days, Leukocytes (cell/mcL)
Time frame: 15 days
Daily total blood count Platelets
Total blood count measured in venous blood for 15 days, platelets (cell/mcL)
Time frame: 15 days
Daily indices of organ damage Liver
ALT U/L in venous blood
Time frame: 15 days
Indices of inflammation C-reactive protein
C-reactive protein microg/L in venous blood
Time frame: day 1, 2, 7, 15
Indices of haemostasis PT
PT ratio in venous blood by treatment arm
Time frame: day 1, 2, 7,15
Daily progression at imaging (chest-X-ray)
progression of lung infiltrates as detected by chest-X-ray by treatment arm
Time frame: 15 days
Major bleeding
Major and/or clinically relevant bleeding according to International Society of Thrombosis and Haemostasis (ISTH) bleeding scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.
Time frame: day 1, 2, 7, 15, 30
Total bleeding
Total bleeding according to International Society of Thrombosis and Haemostasis (ISTH bleeding) scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.
Time frame: day 1, 2, 7, 15, 30
Unexpected clinical or laboratory findings
Number of unexpected changes in clinical or laboratory findings not included in the predefined list of outcomes during treatment. .
Time frame: day 1, 2, 7, 15
Indices of inflammation D-dimer
D-dimer microg/L in venous blood
Time frame: day 1, 2, 7, 15
Indices of inflammation Fibrinogen
Fibrinogen g/L in venous blood
Time frame: day 1, 2, 7, 15
Indices of inflammation IL-6
Interleukin (IL)-6 pg/mL in venous blood by treatment arm
Time frame: day 1, 2, 7, 15
Indices of inflammation IL-1
Interleukin (IL)-1 pg/mL in venous blood by treatment arm
Time frame: day 1, 2, 7, 15
Daily indices of organ damage kidney
serum creatinine micromol/L by treatment arm
Time frame: 15 days
Daily indices of organ damage heart
troponin t ng/L by treatment arm
Time frame: 15 days
Haemostasis aPTT
aPTT ratio by treatment arm
Time frame: day 1, 2, 7,15
Haemostasis VASP PRI
Vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) % by treatment arm
Time frame: day 1, 2, 7,15
Haemostasis platelet-leukocytes aggregates
Platelet-leukocytes aggregates % in peripheral by treatment arm
Time frame: day 1, 2, 7,15
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Azienda Ospedaliera Universitaria Integrata Verona