E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022001 |
E.1.2 | Term | Influenza (epidemic) |
E.1.2 | System Organ Class | 100000004862 |
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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 determine whether a low-dose of steroids (dexamethasone) given at the time of hospital admission for 5 days to adults hospitalised with influenza infection during a pandemic is beneficial. The primary objective of the trial will be whether dexamethasone, given in addition to standard care reduces the number of deaths or reduces the number of admissions to intensive care. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the trial is to determine whether dexamethasone, given in addition to standard care reduces length of hospital stay, hospital readmission and/or post-discharge GP consultations. The trial will also evaluate cost-effectiveness of the intervention. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The mechanistic sub-study is detailed within Appendix B of the main ASAP trial protocol.
This mechanistic sub-study aims to address the following key questions in the treatment of influenza: a)For each patient, what was the point in the natural history of influenza infection at which admission occurred? b)What effect dose steroid have on the natural history of influenza infection defined by clinical phenotype and RNA transcriptomic pattern? c)Does comparison of the transcriptomic pattern in placebo versus steroid treated arm suggest pro-inflammatory and anti-inflammatory mechanisms are both altered?
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E.3 | Principal inclusion criteria |
This trial will be activated in the event of a pandemic. Trial activation will be decided by the NIHR in close discussion with the Trial Steering Committee, the Chief Investigators of the 8 NIHR Pandemic Portfolio studies and the Department of Health. The following inclusion criteria will apply when the trial is activated:
During an influenza pandemic, patients are eligible for the entry into the trial if they: 1)are aged ≥ 16 years 2)have been admitted to hospital within the previous 24 hours with a clinical diagnosis of an influenza-like illness and 3)have given consent
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E.4 | Principal exclusion criteria |
Patients are not eligible for the study if ANY of the following apply at the time of admission to hospital: 1)known to be taking oral or intravenous corticosteroid treatment 2) require treatment with oral or intravenous corticosteroids upon admission to hospital as standard treatment for comorbid illness. 3) known to be on insulin or oral medication for the treatment of diabetes mellitus 4) known contra-indication to dexamethasone or any of the excipients |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is admission to intensive care unit or death, within 30 days of admission to hospital. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 30 (Day 1 = day of hospital admission) |
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E.5.2 | Secondary end point(s) |
1. Length of stay in intensive care unit 2. Readmission within 30 days of hospital discharge 3. GP consultations within 30 days of hospital discharge 4. Length of stay in hospital 5. Death within 30 days of admission to hospital 6. Admission to intensive care unit within 30 days of admission to hospital
The full statistical analysis plan for this trial includes the flexibility to allow for pandemics of different severity. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Length of stay will be evaluated when the patient is discharged from hospital, or at Day 60 if the patient remains hospitalised at Day 60. |
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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 | No |
E.6.4 | Safety | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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 | 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 | 50 |
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 | Yes |
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
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The end of trial is the date of receipt of the last follow-up information (questionnaire or, for any patient hospitalised more than 60 days, the date of obtaining outcome data from hospital-based system records). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 11 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 11 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 1 |