E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PRE-EXPOSURE PROPHYLAXIS WITH HYDROXYCHLOROQUINE IN SANITARIES HIGHLY EXPOSED TO COVID-19 |
PROFILAXIS PRE-EXPOSICIÓN CON HIDROXICLOROQUINA EN SANITARIOS ALTAMENTE EXPUESTOS A COVID-19 |
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E.1.1.1 | Medical condition in easily understood language |
PRE-EXPOSURE PROPHYLAXIS WITH HYDROXYCHLOROQUINE IN SANITARIES HIGHLY EXPOSED TO COVID-19 |
PROFILAXIS PRE-EXPOSICIÓN CON HIDROXICLOROQUINA EN SANITARIOS ALTAMENTE EXPUESTOS A COVID-19 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 assess the efficacy and safety of 155 mg of hydroxychloroquine base as prophylaxis in health professionals subjected to repeated exposures to the COVID-19 virus, to reduce the contagion measured as development of Ig M antibodies. Professionals must be negative for the disease at the beginning of the randomized study. |
Valorar la eficacia y seguridad de 155 mg de hidroxicloroquina base como profilaxis en profesionales sanitarios sometidos a repetidas exposiciones al virus COVID-19, para disminuir el contagio medido como desarrollo de anticuerpos Ig M. Los profesionales han de ser negativos para la enfermedad al inicio del estudio aleatorizado. |
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E.2.2 | Secondary objectives of the trial |
Assess whether there are differences between the two groups in the severity of the disease if IgM antibodies appear. Gravity will be measured as: o Duration of symptoms o Development of viral pneumonia o Specify hydroxychloroquine dose increase o Increased antiviral medication (kaletra ... etc) during the study. o Need for hospital admission o ICU admission Assess the clinical safety of hydroxychloroquine in subjects without comorbidities and its QTc lengthening effect. Assess in both groups whether the appearance of Ig G antibodies protects against the new appearance of disease understood as the appearance of new IgM antibodies in the period studied. Estimation of the percentage of these toilets that have been able to pass the oligosymptomatic disease (Ig M or Ig G positive) in the initial sampling of healthy candidates. |
Valorar si existen diferencias entre los dos grupos en la gravedad de la enfermedad en caso de presentar aparición de anticuerpos IgM. La gravedad será medida como : o Duración de los síntomas o Desarrollo de neumonía viral o Precisar aumento de dosis de hidroxicloroquina o Aumento de medicación antiviral (kaletra…etc) durante el estudio. o Necesidad de ingreso hospitalario o Ingreso en UCI Valorar la seguridad clínica de la hidroxicloroquina en sujetos sin comorbilidades y su efecto de alargamiento del QTc. Valorar en ambos grupos si la aparición de anticuerpos Ig G protege frente a la nueva aparición de enfermedad entendida como aparición de nuevos anticuerpos IgM en el periodo estudiado. Estimación de porcentaje de estos sanitarios que han podido pasar la enfermedad oligosintomáticos (Ig M o Ig G positivo) en el muestreo inicial de candidatos sanos. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Sanitary with high exposure to COVID-19 with training of doctor or DUE belonging to the health network of Navarra 2. No previous diagnosis of COVID-19 3. Not present symptoms compatible with COVID-19, neither present nor past 4. Negative Ig M or Ig G negative immunochromatography test result for both 5. You agree not to self-medicate with chloroquine, hydroxychloroquine, or other potential antivirals. 6. That they give their written informed consent to participate in the trial 7. Not being pregnant. To do this, if you suspect that you might be, you should have previously had a pregnancy test. |
1. Sanitario con alta exposición a COVID-19 con formación de médico o DUE perteneciente a la red sanitaria de Navarra 2. No diagnóstico previo de COVID-19 3. No presentar síntomas compatibles con COVID-19 ni presentes ni pasados 4. Resultado de test rápido de inmunocromatografía de Ig M o Ig G negativo para ambos 5. Consiente no automedicarse con cloroquina , hidroxicloroquina ni otros potenciales antivirales. 6. Que otorguen su consentimiento informado por escrito para participar en el ensayo. 7. No estar embarazada, para ello si sospecha que pudiera estarlo deberá realizarse previamente un test de embarazo. |
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E.4 | Principal exclusion criteria |
1. Hypersensitivity to chloroquine or derivatives. 2. Contraindication to taking hydroxychloroquine (for epilepsy, severe kidney failure (clearance <10 ml / min), severe liver failure). 3. Known retinopathy. 4. Impossibility to continue in the trial during the 6 weeks of treatment. 5. Taking concomitant contraindicated medication: aremeter / lumefantrine and mefloquine as antimalarials, natalizumab, pimecrolimus and tacroliums, moxifloxacin, agasidase alfa and beta, dapsone, tratuzumab, drugs that lengthen QT such as digoxin, amiodarone and some beta blockers. 6. Pregnancy or pregnancy wish in the next 6 weeks. 7. Glucose 6-Phosphate Dehydrogenase deficiency that generates hereditary hemolytic anemia. |
1. Hipersensibilidad a la cloroquina o derivados. 2. Contraindicación de la toma de hidroxicloroquina (por epilepsia, insuficiencia renal grave (aclaramiento <10 ml/min) , insuficiencia hepática grave). 3. Retinopatía conocida. 4. Imposibilidad de continuar en el ensayo durante las 6 semanas de tratamiento. 5. Toma de medicación contraindicada concomitante : aremeter/lumefantrina y mefloquina como antimaláricos, natalizumab, pimecrolimus y tacroliums, moxifloxacino, agasidasa alfa y beta, dapsona, tratuzumab, fármacos que alargan QT como digoxina, amiodarona y algunos beta bloqueantes. 6. Embarazo o deseo de embarazo en las próximas 6 semanas. 7. Déficit de Glucosa 6-Fosfato-Deshidrogenasa que genera anemia hemolítica hereditaria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Appearance of Ig M in rapid test YES / NO Appearance of Ig G in rapid test YES / NO Appearance of symptoms compatible with COVID-19: fever, cough, odynophagia, vomiting or diarrhea, headache, anosmia or hyposmia, ageusia or dysgeusia without any other alternative diagnosis Positive PCR with compatible symptoms carried out in occupational risks (YES / NO) |
Aparición de Ig M en test rápido SI/NO Aparición de Ig G en test rápido SI/NO Aparición de síntomas compatibles con COVID-19: fiebre, tos, odinofagia, vómitos o diarrea, cefalea , anosmia o hiposmia, ageusia o disgeusia sin otro diagnóstico alternativo PCR positivo con síntomas compatibles realizado en riesgos laborales (SI/NO) |
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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) |
Pneumonia compatible with COVID-19 YES / NO Days duration symptoms compatible with COVID19 Increased hydroxychloroquine YES / NO Increased dose of hydroxychloroquine (0 = no change from group assigned 1 = 0 to 200mg Hcl / day; 2 = 200 to 400 mg Hcl / day; 3 = 0 to 400mg Hcl / day) Treatment with lopinavir / ritonavir (Kaletra ) YES / NO Corticosteroid treatment YES / NO Income for pneumonia YES / NO Number of days of admission ICU admission YES / NO Number of days of ICU admission Elongation of the QTc in the second ECG (> 460 msg) (third week of the study) Number of weekly hours worked Reinfection measured as positive Ig M after presenting Ig G YES / NO Percentage Ig M or Ig G positive in the initial sample of candidates without self-perceived symptoms of COVID-19 excluded to participate in the study for this reason. |
Neumonía compatible con COVID-19 SI/NO Días duración síntomas compatible con COVID19 Aumento de hidroxicloroquina SI/NO Dosis de aumento de hidroxicloroquina ( 0=sin cambios respecto a grupo asignado; 1 = de 0 a 200mg Hcl /día ; 2= de 200 a 400 mg Hcl/día; 3 = de 0 a 400mg Hcl/día) Tratamiento con lopinavir/ritonavir (Kaletra ) SI/NO Tratamiento con corticoides SI/NO Ingreso por neumonía SI /NO Número de días de ingreso Ingreso en UCI SI/NO Número de días de ingreso en UCI Alargamiento del QTc en el segundo ECG (>460 msg) (tercera semana del estudio) Número de hora semanales trabajadas Reinfección medida como Ig M positivo tras haber presentado Ig G SI/NO Porcentaje Ig M o Ig G positivos en la muestra inicial de candidatos sin síntomas autopercibidos de COVID-19 excluidos para participar en el estudio por dicho motivo |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
SIN TRATAMIENTO/PROFILAXIS |
WITH OUT TREATMENT/PROPHYLAXIS |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 will be terminated when all patients have completed the follow-up period. However, it may be interrupted prematurely. Circumstances justifying discontinuation of the study include, but are not limited to: Determination of unforeseen, considerable or unacceptable risks for patients. Impossibility of enrolling an acceptable number of patients. Breach of protocol requirements. Failure to comply with the rules of Good Clinical Practice or current legislation |
El ensayo se dará por finalizado cuando todos los pacientes hayan concluido el periodo de seguimiento. No obstante, podrá ser interrumpido prematuramente. Determinación de riesgos imprevistos, considerables o inaceptables para los pacientes. Imposibilidad de inscribir a un número aceptable de pacientes. Incumplimiento de los requisitos del protocolo. Incumplimiento de las normas de Buena Práctica Clínica o legislación vigente. |
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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 | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |