Influenza
Conditions
Brief summary
Clinical trial with an active ingredient of a pharmaceutical specialty marketed in Spain vs. placebo. Randomized, double-blind, multicenter phase III clinical trial that evaluates the efficacy and safety of dexamethasone compared to placebo in patients with severe influenza.
Interventions
DRUGGrup 1 placebo
placebo 1 capsule (6 mg) /day for 7 days.
DRUGGrup 2 dexametasona
dexamethasone 1 capsule (6 mg)/day for 7 days
Sponsors
Instituto de Investigación Sanitaria y Biomédica de Alicante
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
1. Aged ≥ 18 years. 2. 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). 3. Hospitalized patients with an estimated hospital stay of more than 24 hours. 4. In previous treatment or concomitant start of treatment with oseltamivir. 5. For women of childbearing age, use of contraceptive methods until day 30 after completion of treatment. 6. Signed informed consent.
Exclusion criteria
* 1\. Patients with bronchial hyperresponsiveness that requires systemic corticosteroids for more than 24 hours. 2\. 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). 3\. Inability to administer oral oseltamivir. 4. Patients on ECMO (extracorporeal membrane oxygenation). 5. Pre-existing condition or use of medication that, in the opinion of the local investigator, may pose a risk for the administration of corticosteroids. 6\. Patients with severe comorbidity with life expectancy of less than six months in the opinion of the investigator. 7\. Patients co-infected with SARS-CoV-2 or RSV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To compare the percentage of patients hospitalized | 10 days | To compare the percentage of patients hospitalized with influenza according to treatment arm (oseltamivir-dexamethasone vs oseltamivir-placebo) with status 3 or higher according to the Hospital Recovery Scale (status 3: hospitalization with supplemental oxygen, or 4: ICU admission without invasive mechanical ventilation, or 5: with invasive mechanical ventilation, or 6: death) on day 7 after the start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The National Early Warning Score | 10 days | To compare the time, in days, between initiation of treatment and clinical stability according to the NEWS2\<2 scale for 24 hours or until hospital discharge, taking the value of the first of the two events to occur |
| Common Terminology Criteria for Adverse Events (CTCAE) scale | 10 days | To compare the frequency of serious adverse effects between groups (grades 3, 4 and 5 on the CTCAE scale). |
| Rate of metabolic impact of dexamethasone | 10 days | To evaluate the metabolic impact of dexamethasone by comparing the function of occurrence of sustained hyperglycemia level 1 and 2, and episodes of hyperglycemia during and at the end of dexamethasone treatment. |
| Number of pacients in ICU admission | 10 days | To compare the function of occurrence over time of clinical failure, defined as progression to: need for ICU admission, need for intubation or death. |
| mortality | 90 days | To compare mortality at days 10, 30 and 90 post-randomization. |
| the impact of treatment Barthel Index | 90 days | To evaluate the impact of treatment on dependency (Barthel Index) at the time of discharge or at the end of treatment, and at 30 and 90 days after randomization. The final score ranges from 0 to 100, with 100 being the maximum independence and 0 being the maximum dependence. |
| the impact of treatment Clinical Frailty Score | 90 days | To evaluate the impact of treatment on frailty (Clinical Frailty Score) at the time of discharge or at the end of treatment, and at 30 and 90 days after randomization. . level descriptions and their corresponding labels. Most notably, CFS level 2 changed from Well to Fit, level 4 from Vulnerable to Living with Very Mild Frailty, and levels 5-8 were restated as Living with... mild, moderate, severe, and very severe frailty, respectively |
| the average hospital stay | 10 days | To compare the average hospital stay (expressed in days) according to treatment group. |
| the kinetics of influenza virus in nasopharyngeal swabs using Ct | 10 days | To evaluate the kinetics of influenza virus in nasopharyngeal swabs (using Ct and ) in both groups. |
| the kinetics of influenza virus in nasopharyngeal swabs using viral quantification per human cell | 10 days | To evaluate the kinetics of influenza virus in nasopharyngeal swabs (viral quantification per human cell) in both groups. |
| Evaluation inflammatory markers CRP | 10 days | Evaluation the impact of treatment on inflammatory markers CRP |
| Evaluation inflammatory markers PCT | 10 days | Evaluation the impact of treatment on inflammatory markers PCT |
| Evaluation inflammatory markers IL-6 | 10 days | Evaluation the impact of treatment on inflammatory markers IL-6 |
| Evaluation inflammatory markers IL-10 | 10 days | Evaluation the impact of treatment on inflammatory markers IL-10 |
| To evaluate the impact of steroid treatment on the evolution of the nasal microbiome expressed in alpha diversity. | 10 days | To evaluate the impact of steroid treatment on the evolution of the nasal microbiome expressed in alpha diversity. Using NGS and then the consecutive bioinformatic analysis. More specifically, the alpha diversity would be the result of the Shannon Index and the number of ASVs (Amplicon sequence variant). |
Countries
Spain
Contacts
Primary ContactJavier Mateo, Biologist
Backup ContactLivia Giner
Outcome results
None listed