BETAMETHASONE SODIUM PHOSPHATE for Severe influenza|Influenza A or B infection

Inclusion criteria

• {"criterion_text":"- Aged ≥ 18 years.\n- Diagnosis of influenza A or B virus infection by antigen or RT-PCR (local laboratory) at the time of entry or at 48 hours prior to randomization in respiratory specimens (nasopharyngeal swab or bronchoalveolar lavage).\n- Hospitalized patients with an estimated hospital stay of more than 24 hours.\n- In previous treatment or concomitant start of treatment with oseltamivir.\n- For women of childbearing age, use of contraceptive methods until day 30 after completion of treatment.\n- Signed informed consent."}

Exclusion criteria

• {"criterion_text":"- Patients with bronchial hyperresponsiveness that requires systemic corticosteroids for more than 24 hours.\n- Pre-inclusion treatment with corticosteroids for more than 24 hours at a dose equal to or higher than 1 mg/kg methyl-prednisolone (0.2 mg/kg dexamethasone or 1.25 mg/kg prednisone).\n- Inability to administer oral oseltamivir.\n- Patients on ECMO (extracorporeal membrane oxygenation).\n- Pre-existing condition or use of medication that, in the opinion of the local investigator, may pose a risk for the administration of corticosteroids.\n- Patients with severe comorbidity with life expectancy of less than six months in the opinion of the investigator.\n- Patients co-infected with SARS-CoV-2 or RSV."}

Primary endpoints

• {"endpoint_text":"- Percentage of patients in status greater than or equal to 3 (3,4,5 or 6) according to the Hospital Recovery Scale (HRS) on day 7 after the start of treatment.","definition_or_measurement_approach":"Measured as the percentage of patients with Hospital Recovery Scale (HRS) status ≥3 on day 7 after start of treatment. HRS status definitions referenced: status 3 - hospitalization with supplemental oxygen; status 4 - ICU admission without invasive mechanical ventilation; status 5 - with invasive mechanical ventilation; status 6 - death."}

Secondary endpoints

• {"endpoint_text":"- Time elapsed in days between the start of treatment and clinical stability, defined by NEWS-2<2 scale for >24 hours or hospital discharge (first event).","definition_or_measurement_approach":"Time in days from treatment initiation to clinical stability defined as NEWS-2 < 2 sustained for >24 hours or hospital discharge; the first of these events is taken."}
• {"endpoint_text":"- Hospital stay: expressed in days, taken from the discharge date and date of admission.","definition_or_measurement_approach":"Calculated as days between admission date and discharge date."}
• {"endpoint_text":"- Admission to the ICU: from any cause, and related or not to influenza (or its secondary complications) in the opinion of the researcher. Discharge date and date of admission.","definition_or_measurement_approach":"Record of ICU admission regardless of cause as judged by investigator; capture admission and discharge dates."}
• {"endpoint_text":"- Need or not for non-invasive mechanical ventilation (NIMV), with the start/end date.","definition_or_measurement_approach":"Binary recording of requirement for NIMV and documentation of start and end dates."}
• {"endpoint_text":"- Need or not for invasive mechanical ventilation (IMV) with the admission/discharge date.","definition_or_measurement_approach":"Binary recording of requirement for IMV and documentation of admission and discharge dates related to IMV."}
• {"endpoint_text":"- Death: death from any cause, whether or not related to influenza (or its complications) in the opinion of the investigator.","definition_or_measurement_approach":"All-cause mortality as recorded by investigator, with date of death."}
• {"endpoint_text":"- Clinical failure: defined as clinical progression requiring admission to the ICU, invasive mechanical ventilation or death (from any cause) within 72 hours after the start of treatment in the control or experimental arm. Date.","definition_or_measurement_approach":"Occurrence of ICU admission, need for invasive mechanical ventilation, or death within 72 hours of treatment start; date recorded."}
• {"endpoint_text":"- Dependency index: measured with the Barthel index with a score from 0 to 100. Questionnaire that evaluates individual capabilities in 10 basic activities of daily living (Annex IV.-C). It will be measured at the baseline visit (with reference to the 15 days prior to admission), at the end of treatment or at hospital discharge (whichever comes first) and at follow-up visits 30 and 90.","definition_or_measurement_approach":"Barthel Index score (0-100) assessed at baseline (referring to 15 days prior to admission), end of treatment or discharge, and at 30- and 90-day follow-ups."}
• {"endpoint_text":"- Frailty index: measured by the Rockhood scale or Clinical Frailty Score that classifies on a scale of 1 to 8 according to the level of dependency and which serves as a global clinical measure of physical fitness and frailty (Annex IV.-D). It will be measured at the baseline visit (with reference to the 15 days prior to admission), at the end of treatment or at hospital discharge (whichever comes first) and at follow-up visits 30 and 90.","definition_or_measurement_approach":"Clinical Frailty Score (Rockwood) measured at baseline, end of treatment or discharge, and at 30- and 90-day follow-ups; scale 1-8."}
• {"endpoint_text":"- Evaluation of the impact of steroid treatment on the nasal microbiome: evaluation of alpha diversity variation (using Index of Shannon, number of ASV's) and determination of the differential taxa based on the outcome variables on day 10 post-randomization with respect to the baseline determination (Annex VI).","definition_or_measurement_approach":"Assessment of nasal microbiome alpha diversity (Shannon index, number of ASVs) and differential taxa at day 10 vs baseline."}
• {"endpoint_text":"- Shannon index, defined as the quantification index of diversity and richness of microbial species, evaluates quantity and equity of its distribution.","definition_or_measurement_approach":"Shannon index used to quantify diversity and richness of microbial species; used as microbiome outcome measure."}
• {"endpoint_text":"- Amplicon Sequence Variants (ASV's), defined as specific DNA sequence obtained from techniques of massive sequencing and that identifies different taxa.","definition_or_measurement_approach":"Number and identity of ASVs determined by high-throughput sequencing; used to identify taxa."}
• {"endpoint_text":"- Evaluation of viral kinetics: quantification of viral load by Ct (cycle number 10-40) and total RNA/mcg DNA copies at basal level, day 2, 5 and 10 (Annex VI).","definition_or_measurement_approach":"Quantification of viral load by Ct values (cycles 10-40) and RNA copies per mcg DNA at baseline and on days 2, 5 and 10."}
• {"endpoint_text":"- Evaluation of the impact of inflammation markers: measurement of leukocytes, lymphocytes, CRP, PCT (optional), total number of leukocytes and lymphocytes, IL-1 and IL6 will be carried out at baseline, day 2, 5, 7 and 10 (Annex VI).","definition_or_measurement_approach":"Measurement of listed inflammatory markers (leukocytes, lymphocytes, CRP, optional PCT, IL-1, IL-6) at baseline and days 2, 5, 7 and 10."}

Spain

Earliest CTIS Part Ii Submission Date

26-09-2024

Latest Decision Or Authorization Date

27-10-2025

Processing Time Days

396

Number Of Sites

11

Number Of Participants

486

Primary sponsor

Full Name

Fundacion De La Comunitat Valenciana Para La Gestion Del Instituto De Investigacion Sanitaria Y Biomedica De Alicante

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain