E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This trial will investigate infection with coronavirus (COVID-19) in patients who are admitted to hospital |
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E.1.1.1 | Medical condition in easily understood language |
This trial will investigate infection with coronavirus in patients who are admitted to hospital
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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 | 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070255 |
E.1.2 | Term | Coronavirus test positive |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 |
In patients who are admitted urgently to hospital with coronavirus infection (COVID-19) and symptoms, treatment with virus-modifying agent Hydroxyhloroquine as well as virus-immunomodulatory and antibacterial drug Azithromycin can lead to a shorter hospitalization. |
Hos patienter der indlægges akut og som har en positiv test for 2019-nCoV og symptomer svarende til COVID-19 sygdom, kan behandling med virus-modificerende stof hydroxychloroquin samt virus-immunmodulerende og antibakterielle stof azithromycin føre til kortere indlæggelse. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to clarify whether the patients riscs of non-invasive ventilation, intensive care unit admittance and death can be reduced by hydroxychloroquine and azithromycine treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients admitted to a danish emergency department or department of respiratory medicine or internal medicine - Age >18 år - Hospitalized <48 hours - Positive COVID-19 test/diagnosis during hospitalization - fertile women must present a negative pregnancy test - signed informed consent |
• Patient indlagt på en dansk akutmodtagelse, lungemedicinsk afdeling eller medicinsk afdeling • Indlagt <48 timer • Alder >18 år • Positiv COVID-19 test / diagnose under pågældende indlæggelse (bekræftet). • Fertile kvinder skal have negativ graviditetstest • Informeret samtykke underskrevet |
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E.4 | Principal exclusion criteria |
- If the patient uses >5 LO2/min on time of recruitment - Known intolerance/allergy to azithromcyin or hydroxychloroquine - Liver diseases other than amoebiasis - Severe gastrointestinal, neurological and hematological disorders -eGFR <45 ml/min/1.73m2 - Severe cardiac conduction disorders or (risk of) prolonged QT interval - Myasthenia gravis - Neurogenic hearing loss - Psoriasis - Retinopathy - Maculopathy - Visual fiels changes - Breastfeeding - Hypersensitivity to quinine or 4-aminoquinoderivates -Uses Digoxin - Shortage of glucose-6-phosphatedehydrogenase - Porphyria - Hypoglycemia - Severe mental illness which significantly complicates cooperation - Severe linguistic problems that significantly complicates cooperation - Concomitant administration of sickle alkaloids |
• På rekrutteringstidspunktet bruger patienten >5 LO2/min (svarende til 40% FiO2, hvis dette måles) o NB: 5 LO2/min tillades, det er først >5 LO2/min at det er eksklusionsgrund. • Kendt intolerance/allergi overfor azithromycin eller hydroxychloroquin eller Overfølsomhed over for quinin • Neurogen hørenedsættelse • Psoriasis • Retinopati • Makulopati • Synsfeltsforandringer • Amning • Andre svære leversygdomme end amøbiasis (INR>1.5 spontant) • Svære gastro-intestinale, neurologiske og hæmatologiske lidelser (investigator-vurderet) • eGFR<45 ml/min/1.73 m2 Pro-aktiv Beskyttelse af Indlagte patienter med COVID ProBe-COVID-trial 8 • Klinisk betydende kardielle overledningsforstyrrelser/arrytmier eller forlænget QTc interval (QTc(f) på>500 ms. • Myasthenia gravis • Bruger Digoxin • Glucose-6-phosphatedehydrogenasemangel • Porfyri • Hypoglykæmi (Blod-glukose på et hvilket som helst tidspunkt siden indlæggelse på <3.0 mmol/L) • Svær psykisk sygdom som betydeligt vanskeliggør kooperation • Svære sproglige problemer som betydeligt |
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E.5 End points |
E.5.1 | Primary end point(s) |
Days alive and discharged from hospital within 14 days |
• Dage i live og udskrevet fra hospital indenfor 14 dage (opsummerer både om patienten er i live og er udskrevet fra hospital) |
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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) |
Secondary endpoint nr 1: Patient will be categorized within 1 of the following 8 categories on day 15: 1. Dead 2. Admitted, uses mecanical ventilate or ExtraCorporalMembranOxygering (ECMO) 3. Admitted, uses Non-invasive ventilation or "high-flow oxygen device" 4. Admitted, gets oxygen but doesn't live up to (2) or (3) 5. Admitted, no need for oxygen treatment but gets other treatment (COVID related or other) 6. Admitted for observation 7. Discharged, but with limitations of activity level 8. Discharged, no limitations of activity level
- Admitted to intensive care unit then Length of Stay, ICU - has used Non-invasive ventilation (NIV) during hospitalization - death on day 30 - Length of index-hospitalization (days) - days alive and discharged from hospital within 30 days - death on day 90 - death within 12 months - number of readmissions (all causes) within 30 days - number of days of non-invasive ventilation (NIV) - Delta PaO2 day 1 to day 4 - Delta PaCO2 day 1 to day 4 - pH day 4 (72 hours) - Time without oxygen supplement (or regular LTOT oxygen supplement) |
Sekundært endpoint nr 1: Ordinalt outcome. Patienten kategoriseres I en af følgende 8 kategorier på dag 15: 1. Død 2. Indlagt og på mekanisk ventilation eller ExtraCorporalMembranOxygenering (ECMO) 3. Indlagt og på Non-invasiv ventilation eller ”high-flow oxygen device” 4. Indlagt og får ilttilskud som ikke lever op til ilttilskud i (2) eller (3) – f.eks. ilt på ”næsebrille” 5. Indlagt og får ikke ilttilskud, men har brug for behandling (COVID-19-relateret eller anden) 6. Indlagt og får ikke ilttilskud, og har ikke brug for behandling (observeres blot) 7. Udskrevet med begrænsning i aktiviteter, kan være fri af ilttliskud eller bruge LTOT (”hjemmeilt”) 8. Udskrevet, ingen begrænsninger i aktiviteter
• Indlagt på intensivafdeling i de to grupper (0 vs. 1) under index indlæggelsen o For patienter indlagt på intensiv afdeling: antal dage på intensiv (Length of stay, ICU) • Har brugt Non-invasiv ventilation, NIV (0 vs. 1) under index indlæggelsen • Død på dag 30 • Dage indlagt på hospital under index-indlæggelsen • Dage i live og udskrevet fra hospital indenfor 30 dage (opsummerer både om patienten er i live og er udskrevet fra hospital) • Død på dag 90 (rapporteres senere) • Død indenfor 12 måneder (rapporteres senere) • Antal genindlæggelser af alle årsager indenfor 30 dage • Antal dage med non-invasiv-ventilation (NIV) eller respiratorbehandling under index indlæggelsen • Delta PaO2 dag 1 (baseline) til dag 4 (72 timer). Der registreres samtidigt ilttilskud og ilt-system • Delta PaCO2 dag 1 (baseline) til dag 4 (72 timer) • pH dag 4 (72 timer) • Tid til intet ilttilskud (eller til vanlig LTOT ilttilskud)
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 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 | 9 |
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 trial ends after the last follow up, which will be 12 months after the last patient is included. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |