E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hospitalized patients with COVID-19 requiring respiratory support |
Pazienti ospedalizzati con COVID-19 accertato con necessità di supporto respiratorio |
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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 | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053983 |
E.1.2 | Term | Corona virus infection |
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 assess the efficacy of the methylprednisolone protocol in improving survival by day 28 compared to the dexamethasone protocol. |
Valutare l'efficacia del protocollo con metilprednisolone nel migliorare la sopravvivenza entro il giorno 28 rispetto al protocollo con desametasone. |
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E.2.2 | Secondary objectives of the trial |
To compare efficacy of the two protocols in achieving: a) Reduction in the need and duration of mechanical ventilation b) Reduction in hospital mortality c) Reduction in the duration of hospitalization d) Reduction in duration of requirement for oxygen supplementation e) Reduction in C-reactive protein levels f) Reduction in disease progression as assessed by WHO clinical progression scale |
Valutano l'efficacia del protocollo con metilprednisolone rispetto al protocollo con desametasone nel raggiungimento di: a) Riduzione della necessità e della durata della ventilazione meccanica b) Riduzione della mortalità ospedaliera c) Riduzione della durata del ricovero d) Riduzione della durata del fabbisogno di integrazione di ossigeno e) Riduzione longitudinale dei livelli di proteina C reattiva f) Riduzione della progressione della malattia basata sulla scala di progressione clinica dell'OMS (WHO clinical progression scale) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a) Able to understand and sign the informed consent form b) SARS-CoV-2 positive on at least one upper respiratory swab or bronchoalveolar lavage c) PaO2 <= 60 mmHg or SpO2 <= 90% or on HFNC, CPAP or NPPV at randomization d) Age >= 18 years old at randomization |
a) In grado di comprendere e firmare il modulo di consenso informato b) Positivo per SARS-CoV-2 su almeno un tampone nasofaringeo o broncolavaggio/lavaggio bronchiolo-alveolare c) PaO2 <= 60 mmHg o SpO2 <= 90% o su HFNC, CPAP o ventilazione a pressione positiva non invasiva (NPPV) alla randomizzazione d) Età >= 18 anni al momento della randomizzazione |
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E.4 | Principal exclusion criteria |
a) On invasive mechanical ventilation (either intubated or tracheostomized) b) Heart failure as the main cause of acute respiratory failure c) On long-term oxygen or home mechanical ventilation d) Decompensated liver cirrhosis e) Immunosuppression (i.e., cancer on treatment, post-organ transplantation, HIV-positive, on immunosuppressant therapy) f) On chronic steroid therapy or other immunomodulant therapy (e.g., azathioprine, methotrexate, mycophenolate, convalescent/hyperimmune plasma) g) Chronic renal failure with dialysis dependence h) Progressive neuro-muscular disorders i) Cognitively impaired, dementia or decompensated psychiatric disorder j) Quadriplegia/Hemiplegia or quadriparesis/hemiparesis k) Do-not-resuscitate order l) Participating in other clinical trial including experimental compound with proved or expected activity against SARS-CoV-2 infection m) Any other condition that in the opinion of the investigator may significantly impact with patient’s capability to comply with protocol intervention n) Refuse to participate in the study or absence of signed informed consent form. |
a) In ventilazione meccanica invasiva (intubato o tracheostomizzato) b) Scompenso cardiaco come causa principale dell'insufficienza respiratoria acuta c) In ossigenoterapia o ventiloterapia domiciliare d) Cirrosi epatica scompensata e) Immunosoppressione (neoplasia attiva, trapianto d'organo, HIV-positivo, terapia immunosoppressiva) f) In terapia steroidea cronica o altra terapia immunomodulante (ad es. azatioprina, metotrexato, micofenolato, plasma iperimmune) g) Insufficienza renale cronica in terapia sostitutiva h) Disturbi neuromuscolari progressivi i) Disturbo psichiatrico scompensato, deficit cognitivo o demenza j) Quadriplegia/emiplegia o quadriparesi/emiparesi k) Ordine di non rianimare (do-not-resuscitate order) l) Partecipazione ad altri studi clinici che riguardino terapie sperimentali con efficacia provata o attesa sull'infezione da SARS-CoV-2 m) Qualsiasi altra condizione che, a giudizio dello sperimentatore, possa influire sulla capacità del paziente di attenersi al protocollo terapeutico n) Rifiuto di partecipare allo studio o assenza del modulo di consenso informato firmato. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Survival proportion at 28 days in both arms |
Proporzione di sopravvissuti a 28 giorni |
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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) |
a) Number of days free from mechanical ventilation (either NPPV or IMV) by study day 28 in both arms b) Number of days of hospitalization among survivors in both arms c) Proportion of patients requiring tracheostomy in both arms d) C-reactive protein level (mg/L) at study day 3, 7 and 14 in both arms e) PaO2/FiO2 ratio (mmHg) at study day 3, 7 and 14 in both arms f) WHO clinical progression scale at study day 3, 7 and 14 in both arms |
a) Numero di giorni liberi da ventilazione meccanica (sia invasiva che non invasiva) al giorno 28 nei due bracci b) Numero di giorni di ospedalizzazione tra i sopravvissuti nei due bracci c) Proporzione di pazienti necessitanti tracheostomia nei due bracci d) Livelli di proteina C reattiva (mg/L) al giorno 3, 7 e 14 nei due bracci e) Rapporto PaO2/FiO2 (mmHg) al giorno 3, 7 e 14 nei due bracci f) WHO clinical progression scale al giorno 3, 7 e 14 nei due bracci |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3, 7, 14, 28 days |
3, 7, 14, 28 giorni |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 57 |
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 | 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 |
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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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28 days from randomization of the last subject |
28 giorni dalla randomizzazione dell'ultimo soggetto |
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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 |