E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pneumonia due to SARS Cov2 (COVID-19) |
Neumonía por SARS Cov2 (COVID-19) |
|
E.1.1.1 | Medical condition in easily understood language |
Pneumonia due to Covid-19 |
Neumonía por Covid-19 |
|
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 compare and evaluate the efficacy of 3 treatment regimens (Hydroxychloroquine in combination with baricitinib, imatinib or lopinavir / ritonavir) in SARS-CoV-2 patients with severe pneumonia requiring admission, considering primary efficacy as time to clinical improvement. |
Comparar y evaluar la eficacia de 3 pautas de tratamiento (Hidroxicloroquina en combinación con baricitinib, imatinib o lopinavir/ritonavir) en pacientes con SARS-CoV-2 con neumonía grave que requieren ingreso, considerando la eficacia primaria como tiempo a mejoría clínica. |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety (serious adverse effects, premature discontinuation of treatment), tolerability and secondary efficacy parameters of the 3 treatment guidelines, understood as: absence of progression to respiratory failure, absence of increased O2 requirements; need for mechanical ventilation; reduction of analytical parameters associated with poor prognosis; radiological progression of the disease on day + 7 of starting treatment; average hospital stay, intensification treatments, such as steroid boluses and tocilizumab, ICU admission,% mortality at the end of follow-up. In addition, in those patients who consent and participate in an additional sub-study, possible biomarkers and genetic markers of susceptibility to SARS-CoV-2 will be evaluated using high-performance techniques with serum DNA from the participants. |
Evaluar la seguridad (efectos adversos grave, discontinuación prematura de tratamiento), tolerabilidad y parámetros secundarios de eficacia de las 3 pautas de tratamiento entendidos como: ausencia de progresión a insuficiencia respiratoria, ausencia de mayores requerimientos de O2; necesidad de ventilación mecánica; reducción de parámetros analíticos asociados a mal pronóstico; progresión radiológica de la enfermedad en el día + 7 de iniciado el tratamiento; estancia media hospitalaria, tratamientos de intensificación, como bolos de esteroides y tocilizumab, ingreso en UCI, % de mortalidad a final de seguimiento. Además en aquellos pacientes que consientan y participen en subestudio adicional se evaluarán posibles biomarcadores y marcadores genéticos de susceptibilidad al SARS-CoV-2 mediante técnicas de alto rendimiento con DNA sérico de los participantes. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Included in protocol v1.1 of 01 April 2020 |
Incluido en protocolo v1.1 del 01 abril 2020 |
|
E.3 | Principal inclusion criteria |
i. Signed informed consent form ii. ≥18 years iii. Confirmed diagnosis Pneumonia Covid19 + iv. ECOG functional state 0 or 1 v. Less than 7 days from onset of symptoms saw. NO contraindication for medication vii. ECG QT <0.4 viii. Adequate liver, kidney and hematological function (or within the safety range to use these drugs) 1. Absolute granulocyte count> 1.5 x 109 / L 2. Absolute platelet count> 100 x 109 / L 3. Hb> 10 g / dL 4. Cr <1.5 mg / dL or Clearance> 50mL / min 5. Bilirubin <3 ULN 6. AST / ALT ≤ 2.5 times ULN |
i. Formulario consentimiento informado firmado ii. ≥18 años iii. Diagnostico confirmado Neumonía Covid19+ iv. Estado funcional ECOG 0 o 1 v. Menos de 7 días desde inicio de los síntomas vi. NO contraindicación para medicación vii. ECG QT < 0.4 viii. Función hepática, renal y hematológica adecuada (o dentro de rango seguridad para utilizar estos fármacos) 1. Recuento absoluto de granulocitos > 1.5 x 109/L 2. Recuento absoluto plaquetas > 100 x 109/L 3. Hb > 10 g/dL 4. Cr < 1.5 mg/dL o Aclaramiento > 50mL/min 5. Bilirrubina < 3 LSN 6. AST/ALT ≤ 2,5 veces LSN |
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E.4 | Principal exclusion criteria |
i. No Covid confirmation ii. No pneumonia iii. Previous treatment with any of the study drugs iv. Concomitant serious medical condition 1. ICC 2. IAM 6 months prior 3. Unstable Angina 4. Cardiomyopathy 5. Unstable Ventricular Arrhythmia 6. uncontrolled HTA 7. Uncontrolled psychotic disorders 8. Serious active infections 9. HIV 10. Active hepatitis 11. Neoplasia in active cancer treatment v. Inability to take oral medication or malabsorption syndrome saw. vi. Inability to comply with study and follow-up procedures vii. History of only relevant thromboembolic or hemorrhagic episodes in the last 6 months viii. Contraindication to any study medication ix. Pregnant women |
i. No confirmación Covid ii. No neumonía iii. Tratamiento previo con alguna de las drogas de estudio iv. Afectación médica concomitante grave 1. ICC 2. IAM 6 meses previos 3. Angina inestable 4. Miocardiopatía 5. Arritmia ventricular inestable 6. HTA no controlada 7. Trastornos psicóticos no controlados 8. Infecciones graves activas 9. VIH 10. Hepatitis activas 11. Neoplasia en tratamiento oncológico activo v. Incapacidad para tomar medicación oral o síndrome de malabsorción vi. Incapacidad para cumplir el estudio y los procedimientos de seguimiento vii. Antecedentes de episodios tromboembólicos o hemorrágicos clínicamente relevantes en últimos 6 meses viii. Contraindicación alguna medicación de estudio ix. Mujeres embarazadas |
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E.5 End points |
E.5.1 | Primary end point(s) |
8.1 Demographics Age Sex Tobacco Alcohol Significant comorbidity - HTA - Cardiovascular disease - DM - COPD - Cancer - Chronic liver disease - I kidney - Known immunosuppression
8.2 Laboratory parameters COVID BIOMARKERS - PCR - Procalcitonin - LDH - Dimero D - Ferritin - IL6 BIOCHEMICAL PARAMETERS - Enzymatic creatinine - ALT - AST - Bilirubin - GGT - F Alkaline - Albumine - Venous lactate - Ultrasensitive Troponin I - Creatin Kinasa (CK)
HEMATOLOGICAL PARAMETERS - White Series - Leukocytes (in absolute value) - Neutrophils (in absolute value) - Lymphocytes (in absolute value) - Neutrophil / lymphocyte ratio - Platelet / lymphocyte ratio - Red Series - erythrocytes - Hb - Platelets - Coagulation - Fibrinogen - Coagulation Study
MICROBIOLOGICAL PARAMETERS - SARS-Cov2 PCR in nasopharyngeal exudate
8.3 Radiodiagnosis - Unilateral, unilobar, bilobar pneumonia ... - Bilateral pneumonia - Resolution infiltrators - Infiltration resolution days - Stabilization - Radiological progression
8.4 Clinical variables - Symptom onset days - Days resolution symptoms - Fever days - Respiratory improvement (days) - Temperature (<38.4 / 38.4-39.4 /> 39.4) * From The The Hscore11 - Organomegaly (No, liver or spleen, both) * From The Hscore11 - Fever - Dry cough - productive cough - Hemoptysis - dyspnea - Asthenia - Myalgia - headache - nausea Vomiting - Diarrhea - Abdominal discomfort - ARDS - I cardiac - FRA - SHOCK - death - Secondary infection - O2 saturation levels. - Need O2, nasal goggles, liters VM non-invasive reservoir Intubation
8.5 Clinical management variables - Hospital stay - ICU admission - No. of registrations |
8.1 Demográficas Edad Sexo Tabaco Alcohol Comorbilidad importante - HTA - Enfermedad cardiovascular - DM - EPOC - Cáncer - Hepatopatía crónica - I renal - Inmunosupresión conocida
8.2 Parámetros de laboratorio BIOMARCADORES DE COVID - PCR - Procalcitonina - LDH - Dimero D - Ferritina - IL6 PARÁMETROS BIOQUIMICOS - Creatinina enzimática - ALT - AST - Bilirrubina - GGT - F Alcalina - Albumina - Lactato venoso - Troponina I ultrasensible - Creatin Kinasa (CK)
PARÁMETROS HEMATOLÓGICOS - Serie Blanca - Leucocitos (en valor absoluto) - Neutrofilos(en valor absoluto) - Linfocitos (en valor absoluto) - Ratio Neutrofilos/linfocito - Ratio plaquetas/linfocito - Serie Roja - Eritrocitos - Hb - Plaquetas - Coagulación - Fibrinógeno - Estudio de Coagulación
PARÁMETROS MICROBIOLÓGICOS - PCR SARS-Cov2 en exudado nasofaríngeo
8.3 Radiodiagnóstico - Neumonía unilateral, unilobar, bilobar… - Neumonía bilateral - Resolución infiltrados - Dias resolución infiltrados - Estabilización - Progresión radiológica
8.4 Variables clínicas - Días inicio de síntomas - Días resolución síntomas - Días fiebre - Mejora respiratoria (días) - Temperatura (<38.4 / 38.4-39.4 / > 39.4)* Del The Hscore11 - Organomegalia (No, hepato o esplneo, ambas)* Del The Hscore11 - Fiebre - Tos seca - Tos productiva - Hemoptisis - Disnea - Astenia - Mialgias - Cefalea - Nauseas - Vómitos - Diarrea - Disconfort abdominal - SDRA - I cardiaca - FRA - SHOCK - Muerte - Infección secundaria - Niveles saturación de O2. - Necesidad O2, gafas nasales, litros VM reservorio NO invasiva Intubación
8.5 Variables de gestión clínica - Estancia hospitalaria - Ingreso UCI - Nº altas |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, 7 days during treatment, day 14, day 35+/-5 and day 70+/-5 |
Basal, 7 días durante tratamiento, día 14, día 35+/-5 y día 70+/-5 |
|
E.5.2 | Secondary end point(s) |
Security variable. The intensity of an AA will be classified according to version 5.0 of the NCI CTCAE. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf |
Variable de seguridad: La intensidad de un AA se clasificará según la versión 5.0 de los CTCAE del NCI. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, 7 days during treatment, day 14, day 35+/-5 and day 70+/- |
Basal, 7 días durante tratamiento, día 14, día 35+/-5 y día 70+/-5 |
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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 | 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 | Yes |
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 | 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 comparador |
No comparator |
|
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
| 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 | No |
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
|
When the sample size has been reached and the last patient included has made the last trial visit |
Cuando se haya alcanzado el tamaño muestral y eñ último paciente incluido haya realizado la última visita del ensayo |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |