E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 viral infection |
Infezione virale da COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
COVID-19 viral infection |
Infezione virale da COVID-19 |
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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 | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084460 |
E.1.2 | Term | COVID-19 treatment |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
The overarching goal of the Master Protocol is to find effective strategies for inpatient management of patients with COVID-19. Therapeutic goals for patients hospitalized for COVID-19 include hastening recovery and preventing progression to critical illness, multiorgan failure, or death. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19.
Potential agents to investigate on this platform include, but are not limited to, Fostamatinib. These agents all impact the host tissue response in COVID-19 via a number of unique mechanisms including potential beneficial effects on the RAAS system and formation of neutrophil extracellular traps. We will evaluate the efficacy of these agents’ ability to impact the host tissue response and improve outcomes in patients hospitalized with COVID-19. |
L’obiettivo generale del protocollo principale è trovare strategie efficaci per la gestione dei pazienti ricoverati con COVID-19. Gli obiettivi terapeutici per i pazienti ricoverati in ospedale per COVID-19 includono accelerare il recupero e prevenire la progressione a malattia critica, insufficienza multiorgano o decesso. Il nostro obiettivo è determinare se la modulazione della risposta del tessuto ospite migliori gli esiti clinici tra i pazienti con COVID-19.
I potenziali agenti da indagare su questa piattaforma includono, a titolo esemplificativo ma non esaustivo, fostamatinib. Questi agenti hanno tutti un impatto sulla risposta del tessuto ospite nel COVID-19 attraverso una serie di meccanismi unici, compresi i potenziali effetti benefici sul sistema RAAS e la formazione di trappole extracellulari dei neutrofili. Valuteremo con quale efficacia questi agenti sono in grado di influire sulla risposta del tessuto ospite e migliorare gli esiti in pazienti ricoverati con COVID-19. |
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E.2.2 | Secondary objectives of the trial |
A further objective is to determine which of the different renin angiotensin aldosterone system (RAAS) agents’ targets and associated mechanisms of action, when added to current best practice and compared to current best practice plus placebo, result in an effective therapeutic approach to the RAAS system in patients infected with SARS-CoV-2. |
A further objective is to determine which of the different renin angiotensin aldosterone system (RAAS) agents’ targets and associated mechanisms of action, when added to current best practice and compared to current best practice plus placebo, result in an effective therapeutic approach to the RAAS system in patients infected with SARS-CoV-2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Hospitalized for COVID-19
2. =18 years of age
3. SARS-CoV-2 infection, documented by: a. a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR b. documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non-NAT tests is maintained in Appendix G.)
4. Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 =92%, or increased supplemental oxygen to maintain SpO2 =92% for a patient on chronic oxygen therapy
5. Symptoms or signs of acute COVID-19, defined as one or more of the following: a. Cough b. Reported or documented body temperature of 100.4o F or greater c. shortness of breath d. chest pain e. infiltrates on chest imaging (x-ray, CT scan, lung ultrasound) |
1. Ricovero ospedaliero per COVID-19
2. Età = 18 anni
3. Infezione da SARS-CoV-2, documentata da: a. un test dell’acido nucleico (NAT) o test equivalente nei 3 giorni precedenti la randomizzazione OPPURE b. documentata mediante NAT o test equivalente più di 3 giorni prima della randomizzazione E malattia progressiva indicativa di infezione da SARS-CoV-2 in corso secondo lo sperimentatore responsabile (per i test non-NAT, saranno consentiti solo quelli ritenuti con specificità equivalente al NAT dal personale del protocollo. Un elenco centrale dei test non-NAT consentiti è conservato nell’Appendice G.)
4. Ipossiemia, definita come SpO2 < 92% in aria ambiente, nuova somministrazione di ossigeno supplementare per mantenere la SpO2 = 92% o aumento dell’ossigeno supplementare per mantenere la SpO2 =92% in un paziente sottoposto a ossigenoterapia cronica
5. Sintomi o segni di COVID-19 acuto, definiti come uno o più dei seguenti: a. Tosse b. Temperatura corporea segnalata o documentata pari o superiore a 100,4oF (38 °C) c. respiro affannoso d. dolore toracico e. infiltrati alla diagnostica per immagini del torace (radiografia, TAC, ecografia polmonare) |
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E.4 | Principal exclusion criteria |
1. COVID-19 symptom onset >14 days prior to randomization 2. Hospitalized for >72 hours prior to randomization 3. Pregnancy 4. Breastfeeding 5. Prisoners 6. End-stage renal disease (ESRD) on dialysis 7. Patient and/or clinical team is not pursuing full medical management (if a patient has a Do Not Resuscitate order that precludes chest compressions in the event of a cardiac arrest but is otherwise pursuing full medical management, he/she is eligible for this trial). 8. The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient
See agent-specific appendices in the full protocol for agent-specific exclusion criteria |
1. Insorgenza dei sintomi di COVID-19 >14 giorni prima della randomizzazione 2. Ricoverato in ospedale per > 72 ore prima della randomizzazione 3. Gravidanza 4. Allattamento al seno 5. Stato di detenzione 6. Malattia renale allo stadio terminale (ESRD) in dialisi 7. Il paziente e/o il team clinico non perseguono una gestione medica completa (se un paziente ha un ordine di non rianimazione che precluda le compressioni toraciche in caso di arresto cardiaco, ma persegua altrimenti una gestione medica completa, è idoneo per questa sperimentazione). 8. Il medico curante prevede l’incapacità di partecipare alle procedure dello studio o la partecipazione non sarebbe nel migliore interesse del paziente
Vedere le appendici specifiche per l’agente nel protocollo completo per i criteri di esclusione specifici per l’agente |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of oxygen-free days at day 28. |
Il numero di giorni senza ossigeno al giorno 28 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Alive and oxygen free at days 14 and 28 • Alive and respiratory failure-free at days 14 and 28 • Alive and free of new invasive mechanical ventilation at 14 and 28 days • In-hospital, 28-day, 60-day and 90-day mortality • WHO 8-point ordinal scale at 14, 28 and 60 days • Support-free days to Day 28, including: Hospital-free days Respiratory failure-free days Ventilator-free days |
• Alive and oxygen free at days 14 and 28 • Alive and respiratory failure-free at days 14 and 28 • Alive and free of new invasive mechanical ventilation at 14 and 28 days • In-hospital, 28-day, 60-day and 90-day mortality • WHO 8-point ordinal scale at 14, 28 and 60 days • Support-free days to Day 28, including: Hospital-free days Respiratory failure-free days Ventilator-free days |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 60 and day 90 |
giorno 60 e giorno 90 |
|
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) | 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 | 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 | 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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
South Africa |
France |
Spain |
Germany |
Italy |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |