Clinical Trial Evaluating the Efficacy and Safety of Dexamethasone Compared to Placebo in Patients With Severe Influenza (FLUDEX)

Randomized, Double-blind, Multicenter, Phase III Clinical Trial Evaluating the Efficacy and Safety of Dexamethasone Compared to Placebo in Patients With Severe Influenza

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.

Study Overview

• Status: Recruiting
• Conditions: Influenza
• Intervention / Treatment: Drug: Grup 1 placebo; Drug: Grup 2 dexametasona

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Javier Mateo, Biologist; Phone Number: 913972 965; Email: mateo_jav@isabial.es
• Study Contact Backup: Name: Livia Giner; Email: l.gineroncina@gmail.com

Study Locations

• Spain
  • Alicante, Spain
    • Recruiting
    • Hospital General Universitario Dr. Balmis de Alicante (centro coordinador)
    • Contact: Juan Cebollada
  • Elche, Spain
    • Recruiting
    • Hospital General Universitario de Elche
    • Contact: Cati Robledano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo 1 capsule (6 mg) /day for 7 days.	Drug: Grup 1 placebo; placebo 1 capsule (6 mg) /day for 7 days.
Active Comparator: dexamethasone; dexamethasone 1 capsule (6 mg)/day for 7 days	Drug: Grup 2 dexametasona; dexamethasone 1 capsule (6 mg)/day for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the percentage of patients hospitalized	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.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The National Early Warning Score	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	10 days
Common Terminology Criteria for Adverse Events (CTCAE) scale	To compare the frequency of serious adverse effects between groups (grades 3, 4 and 5 on the CTCAE scale).	10 days
Rate of metabolic impact of dexamethasone	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.	10 days
the average hospital stay	To compare the average hospital stay (expressed in days) according to treatment group.	10 days
Number of pacients in ICU admission	To compare the function of occurrence over time of clinical failure, defined as progression to: need for ICU admission, need for intubation or death.	10 days
mortality	To compare mortality at days 10, 30 and 90 post-randomization.	90 days
the impact of treatment Barthel Index	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.	90 days
the impact of treatment Clinical Frailty Score	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	90 days
To evaluate the impact of steroid treatment on the evolution of the nasal microbiome expressed in alpha diversity.	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).	10 days
the kinetics of influenza virus in nasopharyngeal swabs using Ct	To evaluate the kinetics of influenza virus in nasopharyngeal swabs (using Ct and ) in both groups.	10 days
the kinetics of influenza virus in nasopharyngeal swabs using viral quantification per human cell	To evaluate the kinetics of influenza virus in nasopharyngeal swabs (viral quantification per human cell) in both groups.	10 days
Evaluation inflammatory markers CRP	Evaluation the impact of treatment on inflammatory markers CRP	10 days
Evaluation inflammatory markers PCT	Evaluation the impact of treatment on inflammatory markers PCT	10 days
Evaluation inflammatory markers IL-6	Evaluation the impact of treatment on inflammatory markers IL-6	10 days
Evaluation inflammatory markers IL-10	Evaluation the impact of treatment on inflammatory markers IL-10	10 days

Collaborators and Investigators

• Sponsor: Instituto de Investigación Sanitaria y Biomédica de Alicante

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 25, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Enzyme Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: FLUDEX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No