E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076502 |
E.1.2 | Term | Viral pneumonitis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To verify the efficacy of the administration of acetylsalicylic acid vs placebo in preventing worsening of clinical outcomes in Covid-19 hospitalized patients |
Verificare l’efficacia della somministrazione di acido acetilsalicilico vs placebo nel prevenire il peggioramento degli outcome clinici nei pazienti ricoverati con diagnosi di Covid-19 |
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E.2.2 | Secondary objectives of the trial |
I. Improvement of clinical indixes, II. Improvement of biomarkers level, III. Improvement of clinical outcomes IV. safety assessment |
I. Miglioramento degli indici clinici, Ii. Miglioramento dei biomarcatori, III. Miglioramento degli esiti clinici IV. verifica della sicurezza |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Hospitalization in a medical area ward dedicated to Covid-19 patients • Positivity by RT_PCR of the search for genetic material of SARS-CoV2 • Covid-19 pneumonia with moderate clinical picture based on clinical parameters • O2 saturation> 94% with maximum FiO2 32% • Respiratory acts <30 / minute • age >18 years • Consent to participate in the study |
• Ricovero ordinario in reparto di area medica dedicato a pazienti Covid-19 • Positività mediante RT_PCR della ricerca di materiale genetico di SARS-CoV2 • Polmonite Covid-19 con quadro clinico moderata in base ai parametri clinici • Saturazione O2 >94% con FiO2 massima 32% • Atti respiratori <30/minuto • Età superiore a 18 anni • Consenso alla partecipazione allo studio |
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E.4 | Principal exclusion criteria |
• Any Antithrombotic treatment including acetylsalicylic acid • Active Bacterial infection • Active or in maintenance therapy neoplasm • Inability to provide consent • Any contraindication to the acetylsalicylic acid use • Active peptic disease • Active Major pathological bleeding • Recent (<30 days) major bleeding • Recent intracranial bleeding • Need to use therapeutic doses of oral anticoagulants or heparins • Need to use combination antiplatelet drugs for clinical indication • Hypersensitivity to acetylsalicylic acid or to any of the excipients • Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) • Severe hepatic insufficiency (Child-Pugh class C). • Severe heart failure (NYHA class 3-4) • Platelet count less than 150000 / mmc • Haemostasis alteration (INR> 1.5, APTT> 1.5) • Plasma fibrinogen <100 mg / dL • Blood pressure >160/100 mmHg • Concomitant treatment with serotonin reuptake inhibitors • Participation in another pharmacological clinical trial |
• Trattamento antitrombotico con qualsiasi farmaco inclusa l’acido acetilsalicilico già in atto per indicazione clinica • Infezione batterica in atto • Neoplasia attiva o in terapia di mantenimento • Impossibilità a fornire un volontario consenso • Qualunque controindicazione all’uso di acido acetilsalicilico • Malattia peptica attiva • Sanguinamento patologico maggiore in atto. • Recente (<30 giorni) sanguinamento maggiore in qualunque sede • Recente sanguinamento intracranico • Necessità di utilizzare dosi terapeutiche di anticoagulanti orali o eparine • Necessità di utilizzare antipiastrinici in associazione per indicazione clinica • Ipersensibilità al principio attivo acido acetilsalicilico o ad uno qualsiasi degli eccipienti • Ipersensibilità a antinfiammatori non steroidei (FANS) • Insufficienza epatica grave (classe C Child-Pugh). • Insufficienza cardiaca grave (classe 3-4 NYHA) • Conta piastrinica inferiore a 150000/mmc • Alterazione dell’emostasi (INR > 1,5, APTT > 1,5) • Fibrinogeno plasmatico <100 mg/dL • Pressione arteriosa superiore a 160/100 mmHg • Concomitante trattamento con inibitori del reuptake di serotonina • Partecipazione ad altra sperimentazione clinica con farmaco |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primaty endpoint is defined as the occurrence of the first of the following events:
- Transfer to ICU with the need for mechanical ventilation - Death from any cause - PaO2 / FiO2 ratio less than 150 mm Hg |
Tale endpoint è definito come l’accadere del primo tra i seguenti eventi
- Trasferimento in Terapia Intensiva con necessità di ventilazione meccanica - Decesso per qualsiasi causa - PaO2/FiO2 minore di 150 mm Hg |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
within 15 days since randomization |
entro 15 giorni dalla randomizzazione |
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E.5.2 | Secondary end point(s) |
IIIa. Clinical progression (combined clinical indexes: ROX index, Sofa score, Apache score) after 7 and after 15 days of treatment
IIIb. Need to perform chest CT scan due to worsening of gas exchange after 7 and after 15 days of treatment
IIIc. Admission to ICU after 7 and after 15 days of treatment
IIId. Need for mechanical ventilation after 7 and after 15 days of treatment
IIIe. Days free from mechanical ventilation after 7 and 15 days of treatment
IIIf. Venous thrombosis / pulmonary embolism or pulmonary thrombosis, deficiency multiorgan (MOF) or cardiovascular event after 7 and 15 days of treatment IIIg. Death IIIh. Discharge for clinical resolution; IIa. Indexes of inflammation (complete blood count with leukocyte count, CRP, D-dimer, chitokines IL-1, IL-6, fibrinogen, albumin) before randomization, after 24 hours and 48 hours, after 7 and after 15 days
IIb. Platelet and haemostatic indexes (serum Thromboxane B2, 11-dehydro Thromboxane XB2 urinary, platelet count, cross-linked platelets, platelet / leukocyte conjugates, plasma P-selectin a and platelet P-selectin expression before randomization, after 24 hours and 48 hours, after 7 and after 15 days
IIc. Coagulation indexes (aPTT and TP) before randomization, after 24 hours and 48 hours, after 7 and after 15 days; Ia.Body temperature (every 24 hours for all 15 days of treatment) Ib. Respiratory acts / minute (every 24 hours for all 15 days of treatment) Ic. Arterial O2 saturation and blood gas analysis (At 7 and 15 days after randomization) Id. blood count with platelet count, cross-linked platelets, platelet morphovolumetry, eosinophil count (every 24 hours for all 15 days of treatment) Ie. Use of oxygen if saturation <92% (every 24 hours for all 15 days of treatment) If. PaO2/FiO2 ratio (every 24 hours for all 15 days of treatment) Ig. Progression of the radiological picture (within 15 days of treatment) Ih. Organ damage indexes (transaminases, troponin, creatinemia) (every 24 hours for all 15 days of treatment); IVa. Major and / or clinically relevant bleeding according to ISTH bleeding scale after 24, 48 hours and after 7 and 15 days of treatment IVb. Total bleeding according to ISTH bleeding scale after 24, 48 hours and after 7 and 15 days of treatment IVc Minor bleeding according to ISTH bleeding scale after 24, 48 hours and after 7 and 15 days of treatment IVd Reduction in platelet count <100,000 / mmc after 24, 48 hours and after 7 and 15 days of treatment IVe Reduction in hemoglobin values ¿¿greater than 2 g / dL after 24, 48 hours and after 7 and 15 days of treatment IVf Blood transfusion after 24, 48 hours and after 7 and 15 days of treatment IVg. Unexpected changes in laboratory clinical exams after 24, 48 hours and after 7 and 15 days of treatment. |
IIIa. Progressione del quadro clinico (indici clinici combinati: ROX index, Sofa score, Apache score) dopo 7 e 15 giorni di trattamento IIIb. Necessità di eseguire TAC torace per peggioramento degli scambi gassosi dopo 7 e 15 giorni di trattamento IIIc. Necessità di trasferimento in terapia intensiva dopo 7 e 15 giorni di trattamento IIId. Necessità di ventilazione meccanica dopo 7 e 15 giorni di trattamento IIIe. Giorni liberi da ventilazione meccanica dopo 7 e 15 giorni di trattamento IIIf. Comparsa di trombosi venosa/embolia polmonare o trombosi polmonare, deficit (multiorgano (MOF) o evento cardiovascolare dopo 7 e 15 giorni di trattamento IIIg. Decesso IIIh. Dimissione per risoluzione del quadro clinico; IIa. Indici di flogosi (emocromo con conta leucocitaria, PCR, D-dimero, chitochine IL-1, IL-6, fibrinogeno, albumina) prima della randomizzazione, dopo 24 ore e 48 ore, dopo 7 e dopo 15 giorni
IIb. Indici piastrinici ed emostatici (Trombossano B2 sierico, 11-deidro Trombossano XB2 urinario, conta piastrinica, piastrine reticolate, coniugati piastrine/leucociti, P-selettina nel plasma a ed espressione P-selettina piastrinica, prima della randomizzazione, dopo 24 e 48 ore, dopo 7 e dopo 15 giorni
IIc. Indici di coagulazione (aPTT e TP) prima della randomizzazione, dopo 24 e 48 ore, dopo 7 e dopo 15 giorni; Ia. Temperatura corporea ogni 24 ore per tutti i 15 giorni di durata del trattamento Ib. Atti respiratori / minuto ogni 24 ore per tutti i 15 giorni di durata del trattamento Ic. Saturazione arteriosa O2 ed emogasanalisi a 7 e 15 giorni Id. Emocromo con conta piastrinica, piastrine reticolate, morfovolumetria piastrinica, conta eosinofili ogni 24 ore per tutti i 15 giorni di durata del trattamento Ie. Uso di ossigeno se saturazione <92% ogni 24 ore per tutti i 15 giorni di durata del trattamento If. Rapporto PaO2/FiO2 ogni 24 ore per tutti i 15 giorni di durata del trattamento Ig. Progressione del quadro radiologico nei 15 giorni di durata del trattamento Ih. Indici di danno d’organo (transaminasi, troponina, creatinemia) ogni 24 ore per tutti i 15 giorni di durata del trattamento; IVa. Emorragie maggiori e/o clinicamente rilevanti secondo ISTH bleeding scale dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento IVb. Emorragie totali secondo ISTH bleeding scale dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento IVc Emorragie minori secondo ISTH bleeding scale dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento IVd Riduzione della conta piastrinica <100000/mmc dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento. IVe Riduzione dei valori di emoblobina superiore a 2 g/dL dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento IVf Ricorso a trasfusione di sangue dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento. IVg. Alterazioni inattese di accertamenti clinici laboratoristici dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
during 15 days of treatment (for details see endpoint); during 15 days of treatment (for details see endpoint); during 15 days of treatment (for details see endpoint); after 24, 48 hours and after 7 and 15 days of treatment. |
durante 15 giorni di trattamento (per maggiore dettaglio vedere endpoint); durante 15 giorni di trattamento (per maggiori dettagli vedere endpoint); durante 15 giorni di trattamento (per maggiori dettagli vedere endpoint); dopo 24, 48 ore e dopo 7 e 15 giorni di trattamento |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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discharge of the last patient |
dimissione dell'ultimo paziente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |