E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Covid-19 infection |
Infezione Covid-19 |
|
E.1.1.1 | Medical condition in easily understood language |
Covid-19 infection |
Infezione Covid-19 |
|
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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 assess the efficacy and safety of Baricitinib in the management of patients admitted for COVID-19 pneumonia |
Valutare l’efficacia e la sicurezza di Baricitinib nel trattamento dei pazienti con polmonite nel contesto di COVID-19 |
|
E.2.2 | Secondary objectives of the trial |
1. To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days 2. To quantify the mortality within 8 days 3. Peripheral capillary oxygen saturation (SpO2) 4. PaO2/FiO2 5. To assess the rate of patients admitted to the ICU 6. To measure the length of hospital stay 7. To quantify 28-day mortality 8. To quantify the rate of re-admission within 28 days 9. To quantify the cumulative incidence and severity of adverse events |
1. Quantificare il tasso di ciascuno tra: alterazione moderata (100<PaO2/FiO2<=200) o severa (PaO2/FiO2<=100) dell’ossigenazione entro 8 giorni 2. Quantificare la mortalità entro 8 giorni 3. Saturazione periferica (SpO2) 4. PaO2/FiO2 5. Valutare il tasso di pazienti ricoverati in ICU 6. Misurare la durata della degenza 7. Quantificare la mortalità a 28 giorni 8. Quantificare il tasso di ulteriore ricovero entro 28 giorni 9. Quantificare l’incidenza cumulativa e la severità degli eventi avversi |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Ability to obtain informed patient consent noting the limitations of existing knowledge regarding Baricitinib’s efficacy and the labeled warning and precautions as the proposed use is outside the approved indication, as well as the presence of known risk of being treated with Baricitinib while the subject of an active infection - informed Consent as documented by signature - patients with a confirmed SARS-CoV-2 pneumonia - adult patients aged 18-74 years old - infiltrates at chest radiography - = 48 hours from admission - c-reactive protein level greater than 10 mg/dl or ferritin level > 900 ug/L - Lymphocyte count less than 1500/mmc - 200 < PaO2/FiO2 = 300 |
Pazienti adulti (18-74 anni) con diagnosi confermata di polmonite con SARS-CoV-2 con infiltrati alla radiografia del torace e con fattori di attivazione flogistica sistemica insorti o peggiorati nonostante la terapia standard ad almeno 48 ore dalla prima valutazione. |
|
E.4 | Principal exclusion criteria |
- 18 years old< age <= 75 years old - concomitant bacterial infection - lymphopenia less than 200/mmc - hemoglobin < 8 g/dl - absolute neutrophil count < 1 x 109 cells/L - requiring continuous positive airway pressure (C-PAP) or mechanical ventilation - sudden clinical deterioration requiring ICU access or palliative care
Exclusion criteria (Drug-related) - known hypersensitivity or allergy to the study drug - Creatinine clearance < 30 mL/min; if the creatinine clearance is between 30 and 60 mL/min the dose of Baricitinib should be reduced to 2 mg/daily - Severe hepatic impairment (no dose adjustment of Baricitinib is required in mild or moderate hepatic impairment) - Pregnant or breast-feeding - Active tuberculosis - Evidence of active HBV (HbsAg positive) or with detectable HCV-RNA, HIV - Ongoing, acute diagnosis of DVT/PE - Previous diagnosis of DVT/PE |
- 18 anni< età <=75 anni - Infezione batterica concomitante - Linfopenia < 200/mmc - Emoglobina < 8 g/dl - Conta assoluta dei neutrofili < 1 x 109 cellule/L - Necessità di ventilazione con pressione positiva continua (c-PAP) o ventilazione meccanica - Deterioramento clinico improvviso richiedente l’accesso in terapia intensiva o cure palliative
Criteri di esclusione (legati al farmaco): - Nota ipersensibilità o allergia al farmaco sperimentale - Clearance della creatinina < 30 mL/min; se la clearance della creatinina è tra 30 e 60 mL/min, la dose di Baricitinib dovrà essere ridotta a 2 mg/die - Compromissione epatica severa (non è necessario un aggiustamento della dose di Baricitinib in caso di alterazione lieve o moderata) - In stato di gravidanza o di allattamento - Tubercolosi attiva - Evidenza di infezione attiva da HBV (HbsAg positività) o con HCV-RNA rilevabile, HIV - Diagnosi di trombosi venosa profonda/embolia polmonare acuta in corso - Precedente diagnosi di DVT/PE |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome of the study will be the response to treatment. A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria (24) or death, whichever occurs first, within 8 days from enrolment. |
La risposta al trattamento. Un paziente viene considerate come responsivo in assenza di un’alterazione moderata o severa dell’ossigenazione (misurata con il rapporto PaO2/FiO2 all’emogas-analisi arteriosa) ed in mancanza di morte, sulla base dell’evento che si verificherà per primo, entro 8 giorni dall’arruolamento. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days 2. To quantify the mortality within 8 days 3. Peripheral capillary oxygen saturation (SpO2) 4. PaO2/FiO2 5. To assess the rate of patients admitted to the ICU 6. To measure the length of hospital stay 7. To quantify 28-day mortality 8. To quantify the rate of re-admission within 28 days 9. To quantify the cumulative incidence and severity of adverse events |
1. Quantificare il tasso di ciascuno tra: alterazione moderata (100<PaO2/FiO2<=200) o severa (PaO2/FiO2<=100) dell’ossigenazione entro 8 giorni 2. Quantificare la mortalità entro 8 giorni 3. Saturazione periferica (SpO2) 4. PaO2/FiO2 5. Valutare il tasso di pazienti ricoverati in ICU 6. Misurare la durata della degenza 7. Quantificare la mortalità a 28 giorni 8. Quantificare il tasso di ulteriore ricovero entro 28 giorni 9. Quantificare l’incidenza cumulativa e la severità degli eventi avversi |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
8 and 28 days |
8 e 28 giorni |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
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
|
|
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 |