E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037373 |
E.1.2 | Term | Pulmonary disorder |
E.1.2 | System Organ Class | 100000004855 |
|
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 |
The overall objective of the study is to evaluate the clinical efficacy and safety of investigational therapeutics relative to the control arm among hospitalized adult patients who have COVID-19.
|
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients 18 years and older • SARS-CoV-2 infection confirmed by PCR in any specimen < 9 days prior to randomization • Admitted to the hospital ward or the ICU due to COVID-19 • SpO2 ≤ 94% on room air OR oxygen demand OR breathing support • Written informed consent obtained |
|
E.4 | Principal exclusion criteria |
• Patient's non-consent or inability to informed consent • Pregnant or breastfeeding women • Subjects pretreated with one of the active study drugs in the past 29 days • Anticipated transfer within 72 hours to a non-study hospital • Severe co-morbidity with life expectancy < 3 months according to investigators opinion • AST or ALT > 5 times the upper limit of normal • Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30 mL/min) • Contraindications to any of the active study drugs • Subjects participating in a potentially confounding drug or device trial during the course of the study in the last 29 days • Any reason why, in the opinion of the investigators, the patient should not participate |
|
E.5 End points |
E.5.1 | Primary end point(s) |
improvement of the clinical status on the ordinal 7-point severity-scale at day 15: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Time to an improvement of one category from admission using the 7-point ordinal scale • Mortality: in-house mortality; 28 days mortality; 90 days mortality • Hospital stay: Duration of hospital stay due to COVID-19 • Oxygen: Need of, time to first receiving and duration of oxygen • Intensive care: Need of, time to first receiving and duration of intensive care • Mechanical ventilation: Need of, time to first receiving and duration of mechanical ventilation • ECMO: Need of, time to first receiving and duration for extracorporal membrane oxygenation • Superinfections • Kidney failure • Myocardial failure • Multiple organ failure |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• day 28 • end of hospital stay • time to receiving intensive care • time to receiving mechanical ventilation • day 90 |
|
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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
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 |
|
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 | 4 |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |