E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe confirmed COVID-19 pneumonia |
Pneumonie sévère confirmée à COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
Severe confirmed COVID-19 pneumonia |
Pneumonie sévère confirmée à COVID-19 |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 100000004862 |
|
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 a management strategy combining a broad panel respiratory mPCR and an algorithm of early antibiotic de-escalation and discontinuation based on both the mPCR results and the procalcitonin, on antibiotics exposure, as compared with a conventional strategy, in severe confirmed COVID-19 pneumonia. |
Evaluer l’efficacité d’une stratégie combinant une PCR multiplex respiratoire FA-PPP et un algorithme de désescalade et d’interruption précoces de l’antibiothérapie basée sur le résultat de la mPCR et sur le dosage de la procalcitonine, sur la durée d’exposition aux antibiotiques, en comparaison à une stratégie conventionnelle au cours de la pneumonie sévère COVID-19. |
|
E.2.2 | Secondary objectives of the trial |
Mortality rates at 28 (D28) and 90 days (D90); - Overall antibiotics use, including broad- and narrow-spectrum antibiotics; - Total exposure to antibiotics at D28; - Number of organ-failure free days at D28; - Incidence rates of bacterial super-infections and colonization/infection with resistant pathogens at D28; - ICU and hospital lengths of stay; - Quality of life at D90. |
Comparer l’efficacité et la sécurité de la stratégie interventionnelle et de la stratégie contrôle, en terme de : - Mortalité à 28 et 90 jours; - Utilisation des Antibiotiques, incluant les antibiotiques à spectre étroit et large; - Exposition totale aux antibiotiques à 28 jours; - Défaillances d’organes à 28 jours; -Incidence des surinfections bactériennes et des colonisations/infections à bactéries multi/hautement résistantes à 28 jours; - Durée de séjour en réanimation et à l’hôpital; - Qualité de vie à 90 jours. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adults (>= 18 years) admitted to the ICU; - Severe confirmed COVID-19 pneumonia, defined by i) a newly-appeared pulmonary parenchymal infiltrate; and ii) a positive RT-PCR (either upper or lower respiratory tract) for COVID-19 (SARS-CoV-2); iii) and admission to the ICU or intermediate care unit; - Informed consent or emergency procedure. |
- Adults (>= 18 years) admitted to the ICU; - Severe confirmed COVID-19 pneumonia, defined by i) a newly-appeared pulmonary parenchymal infiltrate; and ii) a positive RT-PCR (either upper or lower respiratory tract) for COVID-19 (SARS-CoV-2); iii) and admission to the ICU or intermediate care unit; - Informed consent or emergency procedure.
|
|
E.4 | Principal exclusion criteria |
- Pregnancy and breastfeeding women ; - Congenital immunodeficiency; - HIV infection with CD4 count below 200/mm3 or unknown in the last year; - High-grade hematological malignancy; - Neutropenia (<1 leucocyte/mL or < 0.5 neutrophil/mL); - Immunosuppressive drugs within the previous 30 days, including anti-cancer cytotoxic chemotherapy and anti-rejection drugs for organ/bone marrow transplant; - Moribund patient or death expected from underlying disease during the current admission; - Patient deprived of liberty or under legal protection measure. |
Femmes enceintes ou allaitantes ; - Immunodépression congénitale ; - Infection par le VIH avec un taux de CD4 inférieur à 200 / mm3 ou inconnu au cours de la dernière année; - Hémopathie maligne de haut grade évolutive ; - Neutropénie (<1 leucocyte/mL or < 0.5 neutrophil/mL); - Traitement immunosuppresseur au cours des 30 jours précédents, incluant la chimiothérapie anticancéreuse cytotoxique et les médicaments anti-rejet chez le greffé d'organe solide ou de moelle ; - Patient moribond ou décès imminent lié à une maladie préalable ; - Personne privée de liberté ou sous protection juridique.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary assessment criterion is the number of antibiotic free days at D28, which corresponds to the number of days alive without any antibiotic at Day 28. The D28 time point is usual in studies assessing antibiotic use in ICU patients. |
Nombre de jours vivant sans antibiotique à J28.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The secondary assessment criteria are: - Mortality rates at D28 and D90; - Number of defined daily dose (DDD) per 100 patient-days of broad- and narrow-spectrum antibiotics; - Antibiotics duration at D28; - Number of organ-failure free days (based on SOFA) at D28; - Incidence rates of bacterial super-infections at D28; Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28; - ICU and hospital lengths of stay; - Quality of life at D90, assessed using a quality of life questionnaire (EQ5D5L). |
- Taux de mortalité à 28 et 90 jours; - Nombre de defined daily dose (DDD) pour 100 patients-jours pour les antibiotiques à spectres étroit et large; - Nombre de jours d’exposition aux antibiotiques à 28 jours ; - Nombre de jours sans défaillance d’organe (basé sur SOFA) à 28 jours; - Incidence des surinfections bactériennes à 28 jours; -Incidence des colonisations/infections à bactéries multi/hautement résistantes et à C. difficile à 28 jours ; - Durée de séjour en réanimation et à l’hôpital - Qualité de vie à J90, évaluée à l'aide d'un questionnaire sur la qualité de vie (EQ5D5L). |
|
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 | Yes |
E.6.3 | Therapy | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Stratégie conventionnelle |
Conventional strategy |
|
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 | 20 |
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 | No |
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
|
LVLS |
Dernière visite de suivi du dernier patient |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |