E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19; respiratory failure; hypoxaemia. |
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E.1.1.1 | Medical condition in easily understood language |
Coronavirus; breathing difficulties |
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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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001053 |
E.1.2 | Term | Acute respiratory failure |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 | 10021141 |
E.1.2 | Term | Hypoxaemia |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 |
(1) disease progression prior to Day 14 (worsening respiratory failure; defined using severity of hypoxaemia using [PaO2/FiO2 ratio] OR [SpO2/FiO2 ratio]); (2) time to mechanical ventilation prior to Day 14 (or need of). |
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E.2.2 | Secondary objectives of the trial |
(1) Overall survival [up to 28 days after randomisation] (2) Reduction in proportion of patients who require ventilation [to Day 28] (3) Reduction in length of Critical Care stay [to Day 28] (4) Reduction in length of Hospital stay [to Day 28] (5) Modulation of serum pro- and anti-inflammatory cytokines (6) Reduction in duration of ventilation [to Day 28] (7) Increase in ventilator-free days (VFDs) [to Day 28] *The co-primary outcomes will also be repeated as a secondary analysis at Day 28 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged 18 years and above; 2. Hospitalised; 3. Confirmed or suspected SARS-CoV-2 infection; 4. National Early Warning Score (NEWS2) ≥ 3 in a single parameter or NEWS2 > 5 overall; 5. Acute hypoxaemic respiratory failure: PaO2/FiO2 ratio ≤ 300 OR SpO2/FiO2 ratio < 315 (Kigali Modification) 6. Provision of written informed consent by the patient OR by the patient's Legal Representative OR professional consultee. |
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E.4 | Principal exclusion criteria |
1. Any of the following contraindications to ibuprofen: - A known hypersensitivity to ibuprofen or any other constituent of the medicinal product; - Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs); - Patients with a history of, or existing gastrointestinal ulceration/perforation or bleeding, including that associated with NSAIDs; - Patients with severe hepatic failure, defined as Class C (> 9) on the Child-Pugh Classification; - Patients with acute renal failure, defined as ≥ Stage 2 as per the AKIN Criteria; - Patients with severe heart failure, defined using the 2018 criteria of Advanced Chronic Heart Failure from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). - Patients with uncontrolled hypertension. 2. Known use of any other investigational drug less than 30 days prior to study enrolment; 3. Glasgow Coma Score < 12; 4. Patients who cannot swallow oral capsules; 5. Pregnant or lactating women; 6. Any medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
(1) Disease progression prior to Day 14 (worsening respiratory failure – defined using severity of hypoxaemia using [PaO2/FiO2 ratio] OR [SpO2/FiO2 ratio]); (2) Time to mechanical ventilation prior to Day 14 (or need of). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
(1) Overall survival [up to 28 days after randomisation] (2) Reduction in proportion of patients who require ventilation [to Day 28] (3) Reduction in length of Critical Care stay [to Day 28] (4) Reduction in length of Hospital stay [to Day 28] (5) Modulation in serum pro- and anti-inflammatory cytokines (6) Reduction in duration of ventilation [to Day 28] (7) Increase in ventilator-free days (VFDs) [to Day 28] *The co-primary outcomes will also be repeated as a secondary analysis at Day 28 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 |
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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 | 2 |
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 the trial will be defined as database lock. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |