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] - Virus Diseases [C02] |
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 |
To investigate the effect of Remdesivir and Hydroxychloroquine on allcause in-hospital mortality compared to standard of care. |
|
E.2.2 | Secondary objectives of the trial |
- To assess the effect of Remdesivir and Hydroxychloroquine treatment on hospital duration, receipt of ventilation or intensive care, and to identify any serious adverse reactions. - To assess the effect of Remdesivir and Hydroxychloroquine treatment on 28 days mortality, viral clearance, kidney and myocardial failure, coinfections, organ dysfunction and health-related Quality of Life.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult patients, 18 years and above 2. Confirmed SARS-2-CoV-2 infection by PCR 3. Admitted to the hospital ward or the ICU 4. Subjects provides written informed consent prior to initiation of the study 5. No anticipated transfer within 72 hours to a non-study hospital 6. • If heterosexually active, men and women of child bearing potential must practice a highly effective method of birth control, including combined (estrogen and progestogen containing) hormonal prescription oral, intravaginal, transdermal contraceptives, or progestogen containing hormonal prescription oral, injectable, implantable contraceptives or intrauterine device (IUD), or intrauterine hormone-releasing systems (IUS), or male partner sterilization. The above methods of contraception must be agreed to be used up to the last visit, Follow up 3 months.
|
|
E.4 | Principal exclusion criteria |
1. Severe co-morbidity with life expectancy <3 months according to investigators assessment 2. ASAT/ALAT > 5 times the upper limit of normal 3. Acute co-morbidity within 7 days before inclusion such as myocardial infarction 4. Severe renal impairment, defined as an eGFR <40 mL/min 5. Known intolerance to the available study drugs 6. Pregnancy or breast feeding 7. Any reason why, in the opinion of the investigators, the patient should not participate 8. Subject participates in a potentially confounding drug or device trial during the course of the study 9. Prolonged QTc interval (>470 ms) 10. Cardiac heart failure (Ejection Fraction < 40%; uncompensated) 11. Electrolyte disturbances as hypocalcemia <4.65 mg/dL, hypokalemia <3.4 mmol/L, or hypomagnesia <1.7 mg/dL. However, if the electrolyte disturbances are corrected patient may be included with a delayed start of the test drug 12. Patients already receiving any of the study drugs 13. Patients diagnosed with psoriasis or porphyria 14. Patients receiving any of the following medications: dexametasone, haloperidol, carbamazepine, phenytoin, rifampin, phenobarbital, isoniazid, pyrazinamide, nevirapine, ritonavir, phenytoin or sodium valproate/valproic acid.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
All-cause in-hospital mortality. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
During hospitalisation: - Receipt of mechanical ventilation - Time to first receiving and duration of mechanical ventilation - Receipt of intensive care - Duration of intensive care - Occurrence of Suspected Unexpected Serious Adverse Reactions (SUSARs) During hospitalisation: - Viral clearance as assessed by SARS-CoV 2 PCR in peripheral blood and nasopharyngeal and lower airway specimens during hospitalisation - Occurence of kidney failure (eGFR <40) - Occurence of myocardial failure (left ventricular ejection fraction <40 % as assessed by echocardiography) - Occurence of co-infections (super infections with bacteria, fungi and other virus) Assessed during or after 3 months: - Presence of organ dysfunction (i.e. pulmonary, renal, cardiac and cerebral) after 3 months - Quality of Life after 3 months assessed by Version 1.2 of the generic 36-item Short Form Health Survey (SF-36) and the 5-dimension EuroQoL (EQ-5D) questionnaires. - 28 days mortality Exploratory: Biomarkers during hospitalisation • Inflammatory and anti-inflammatory mediators as assessed in serum and plasma • Markers of extracellular matrix remodelling • Markers of endothelial activation Markers of platelet activation Adverse events during hospitalisation |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | Yes |
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 | 3 |
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 | 7 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |