E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with history of SARS-Cov-2 infection and residual respiratory impairment |
Pazienti con storia recente di polmonite COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
patients with history of SARS-Cov-2 infection and residual respiratory impairment |
Pazienti con storia recente di polmonite COVID-19 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 | 10058686 |
E.1.2 | Term | Bilateral pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 investigate the efficacy of NAC in improving diffusion lung capacity of carbon monoxide (DLco) as compared to placebo in patients with recent history of COVID-19 infection. |
- Valutare l’efficacia di NAC in termini di variazione della capacità di diffusione del monossido di carbonio (DLCO) rispetto al placebo in pazienti con storia recente di polmonite COVID-19. |
|
E.2.2 | Secondary objectives of the trial |
• To assess efficacy of NAC on ameliorating tolerance to exercise, pulmonary function, radiological abnormalities, symptoms and quality of life in the selected study population. • To assess the safety and tolerability of NAC administration in the study population. |
- Stabilire l’efficiacia di NAC in termini di tolleranza all’esercizio fisico, funzionalità polmonare, alterazioni radiologiche, sintomi e qualità di vita. - Valutare la sicurezza e tollerabilità di NAC nella popolazione di studio. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age =18 and =90 years. 2. History of hospitalization for COVID-19 pneumonia, as documented by positive RT/PCR testing for SARS-Cov-2 infection (nasopharyngeal swab) and suggestive radiological findings at the chest CT scan. 3. Resolution of SARS-CoV-2 infection as defined by negative RT/PCR testing (nasopharyngeal swab). 4. Evidence of residual interstitial lung abnormalities (including any of the following: ground glass, reticulation, or consolidation with overall extent =5% of total lung volume) on chest high resolution CT scan (performed during screening or within 30 days from screening visit) AND One or more of the following: - DLco = 70 % of predicted value at screening - Oxygen desaturation at 6-minute walk test (6MWT) =4% from baseline value at screening. - Total Lung Capacity = 80 % of predicted value at spirometry performed at screening - Exertional dyspnea at screening, as defined by MMRC =1 |
1. Età =18 e =90. 2. Storia di ospedalizzazione per polmonite COVID-19 3. Risoluzione dell’infezione definita dalla negatività al test RT/PCR per Sars-Cov-2 (tampone nasofaringeo). 4. Evidenza di persistenti alterazioni interstiziali alla TC del torace ad alta risoluzione eseguita durante lo screening o entro 30 giorni dalla visita di screening. In aggiunta ad uno dei seguenti criteri: - DLCO =70% del valore predetto allo screening, - Desaturazione al test del cammino dei 6 minuti (6MWT) =4% allo screening, - TLC =80% del valore predetto allo screening, - Dispnea da sforzo allo screening (MMRC =1). |
|
E.4 | Principal exclusion criteria |
1. Evidence of resting respiratory failure, as defined by PaO2 =60 mmHg (FiO2 21%) at blood gas analysis at screening. 2. History of interstitial lung disease, or evidence of interstitial lung disease at screening that suggests any of the following: idiopathic interstitial pneumonias; lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs; other types of occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including vasculitis, infectious diseases (Other than SARS-Cov-2 infection) and connective tissue diseases. 3. History of other types of respiratory diseases, including disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude the subject’s participation in the study. 4. Any other known disease, medical conditions or blood test abnormalities that in the opinion of the Investigator may put the patient at risk because of participation, interfere with study procedures or cause concern regarding the patient inability to participate in the study. 5. Concomitant treatment with oral corticosteroids and/or other immunosuppressive drugs. 6. Pregnancy status. 7. Incapacity of providing valid informed consent. |
1. Evidenza di insufficienza respiratoria a riposo definita come PaO2 =60 mmHg (FiO2 21%) all’emogasanalisi arteriosa allo screening, 2. Storia di fibrosi polmonare o evidenza di una tra le seguenti patologie respiratorie allo screening: polmonite interstiziale idiopatica o secondaria ad esposizione, a farmaci, granulomatosi, vasculiti, infezioni (non da SARS-Cov-2) e connettivopatie, 3. Storia di altre patologie respiratorie, 4. Qualsiasi altra condizione medica o valori di laboratorio alterati che all'opinione dello sperimentatore possono interferire con la capacità del paziente di partecipare allo studio 5. Assunzione di farmaci steroidei o immunosoppressori, 6. Stato di gravidanza, 7. Incapacità a fornire il consenso informato. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in percent predicted DLco from baseline to week 12 |
Variazione del valore di DLCO in percentuale rispetto al predetto dal baseline a 12 settimane |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Change in absolute (ml/min/mmHg) predicted DLco from baseline to week 12. - Proportion of patients with oxygen desaturation at 6MWT =4% from baseline value at week 12. - Change in St. George’s Respiratory Questionnaire (SGRQ) score from baseline to week 12. - Change in University of California San Diego - Shortness of Breath Questionnaire (UCSD-SOBQ) score from baseline to week 12. - Change in Leicester Cough Questionnaire (LCQ) from baseline to week 12. - Change in FVC (L) from baseline to week 12. - Proportion of patients with improvement of interstitial changes on chest high-resolution computed tomography at 12 weeks, as defined by central radiological review. - Change in Quantitative Lung Fibrosis (QLF) volume from baseline to week 12. |
- Variazione del valore di DLCO in assoluto (ml/min/mmHg) rispetto al predetto dal baseline a 12 settimane. - Proporzione di pazienti con desaturazione al test del cammino =4% dal baseline a 12 settimane. - Variazione del punteggio al questionario St. George’s Respiratory (SGRQ) dal baseline a 12 settimane. - Variazione del punteggio al questionario University of California San Diego - Shortness of Breath Questionnaire (UCSD-SOBQ) dal baseline a 12 settimane. - Variazione del punteggio al questionario Leicester Cough Questionnaire (LCQ) dal baseline a 12 settimane. - Variazione della FVC (L) dal baseline a 12 settimane. - Proporzione di pazienti con miglioramento delle alterazioni interstiziali rilevabili alla TC del torace ad alta risoluzione (HRCT) dal baseline alla settimana 24 dopo revisione centrale. - Variazione del Quantitative Lung Fibrosis (QLF) volume dal baseline a 12 settimane. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |