E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pneumonia caused by COVID-19 |
Neumonía causada por COVID-19 |
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E.1.1.1 | Medical condition in easily understood language |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084381 |
E.1.2 | Term | Coronavirus pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
To study the efficacy and safety of icatibant in adult patients admitted to hospitalization units for pneumonia caused by COVID-19, without mechanical ventilation, 10±1 days after starting treatment or discharge from hospital if this occurs before 10 days. |
Estudiar la eficacia y seguridad del icatibant en pacientes adultos, ingresados en unidades de hospitalización por neumonía causada por COVID-19, sin ventilación mecánica, a los 10±1 días de haber iniciado el tratamiento o alta hospitalaria si ésta sucede antes de los 10 días. |
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E.2.2 | Secondary objectives of the trial |
Clinical: - time to reach a 48-hour clinical response. -time to reach an afebrile state of 48 hours - long term efficacy - role of drug treatments used in the standard of care (SoC) on efficacy and safety. - duration (days) of the hospital stay. - influence of time (days with illness) on the response to treatment. -incidence of complications related to COVID-19 - incidence of relapse of SARS-CoV-2 pneumonia - incidence of re-entry for any reason - incidence of new consultations to the emergency department for any cause - incidence of mortality from Covid-19 - incidence of all-cause mortality Safety: icatibant: SAEs incidence according to severity up to 28±3 from hospital discharge. |
Clínicos: - tiempo hasta alcanzar una respuesta clínica de 48 horas. -tiempo hasta alcanzar un estado afebril de 48 horas. - eficacia a largo plazo - papel de los tratamientos farmacológicos utilizados en el estándar de cuidado (SoC) en la eficacia y seguridad. - duración (días) de la estancia hospitalaria. - influencia del tiempo transcurrido desde el inicio de los síntomas (días con enfermedad) en la respuesta al tratamiento. -incidencia de complicaciones relacionadas con COVID-19 - incidencia de recaída de neumonía por SARS-CoV-2 - incidencia de reingresos por cualquier causa - incidencia de nuevas consultas a urgencias por cualquier causa - incidencia de mortalidad por COVID-19 - incidencia de mortalidad por cualquier causa Seguridad: icatibant:incidencia AAGs según gravedad hasta 28±3 d./alta hospital. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1-adult patients (18 years or older), both sexes 2-Sars-CoV-2 infection confirmed by PCR less than 4 days before randomization 3-hospitalized with a diagnosis of SARS-CoV-2 pneumonia 4-radiographic evidence of pulmonary infiltrates 5-grade 4 or 5 on the ordinal scale for the evaluation of the patient's clinical condition 6-pO2/FiO2 <380 7-men and women of childbearing age who have heterosexual relations must be agreement to use the safe method(s) of contraception 8-obtaining the informed consent of the patient or the legal representative. |
1-pacientes adultos (18 años o más), de ambos sexos 2-infección por SARS-CoV-2 confirmada por PCR menos de 4 días antes de la aleatorización 3-hospitalizados con diagnóstico de neumonía por SARS-CoV-2 4-evidencia radiográfica de infiltrados pulmonares 5-grado 4 ó 5 en la escala ordinal para la evaluación del estado clínico del paciente 6-pO2/FiO2 <380 7-los hombres y mujeres en edad fértil que tienen relaciones heterosexuales deben estar de acuerdo en usar el método o métodos de anticoncepción seguros 8-obtención del consentimiento del paciente o representante legal. |
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E.4 | Principal exclusion criteria |
1-imminent death (life expectancy less than 72h) 2-known hypersensitivity or known adverse reactions to the study drug, or its metabolites or excipients of the formulation 3-invasive mechanical ventilation 4-participation in any other clinical trial 5- ALT or AST > 5 x ULN 6-creatinine clearance <50 mL/min using the Cockcroft-Gault formula for participants '18 years old [Cockcroft 1976] 7-patients with recent acute coronary syndrome (<1 month) 8-patients with a history of stroke 9-positive pregnancy test 10-pregnant or lactating woman |
1-muerte inminente (expectativa de vida menos de 72h) 2-hipersensibilidad conocida o reacciones adversas conocidas al fármaco del estudio, o a sus metabolitos o a excipientes de la formulación 3-ventilación mecánica invasiva 4-participación en cualquier otro ensayo clínico 5- ALT o AST > 5 x ULN 6-eliminación de creatinina <50 mL/min utilizando la fórmula Cockcroft-Gault para participantes `18 años de edad [Cockcroft 1976] 7-pacientes con síndrome coronario agudo reciente (< 1 mes) 8-pacientes con antecedentes de accidente cerebrovascular 9-prueba de embarazo positiva 10-mujer embarazada o lactante |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy and safety will be evaluated 10 (±1) days after the start of treatment or at hospital discharge if before day 10: number of patients reaching grade 2 (inpatient, no longer requiring supplemental oxygen and no longer requiring care or grade 1 (hospital discharge) of the ordinal scale of the clinical state of the patient for 48 hours straight* and who has not had an adverse reaction of 3 or 4 or 5 according to the Criteria of Adverse Event Terminology (CTC-AE of the term in Common Terminology Criteria for Adverse Events). |
La eficacia y seguridad se evaluará a los 10 (±1) días de haber iniciado el tratamiento o al alta hospitalaria si ésta ocurre antes del día 10: número de pacientes que alcanzan el grado 2 (paciente hospitalizado, que ya no requiere oxígeno suplementario y ya no requiere atención médica continua) o grado 1 (alta hospitalaria) de la escala ordinal del estado clínico del paciente durante 48 horas seguidas* y que no haya presentado una reacción adversa de grado 3 ó 4 ó 5 según los Criterios de Terminología de Eventos Adversos (CTC-AE del término en inglés Common Terminology Criteria for Adverse Events). |
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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) |
Clinical: -Number (percentage) of patients who reach grade 2 or grade 1 during the 10 days of to have initiated treatment. - Number (percentage) of patients discharged from hospital who, since discharge The patient must be discharged from the hospital by the 28th day without a relapse or comorbidity related to COVID-19 -Time ('days') until reaching an afebrile state: body temperature less or same as37.5ºC for 48 hours without antipyretic medication -Long-term effectiveness (up to 28 days from discharge, visit 4): "number of patients" who on day 28th of discharge from the hospital continue at grade 2 or grade 1 on the state ordinal scale from the patient's hospital discharge. -Number of days of hospital stay (from the day of initiation of antiviral treatment to discharge from hospital) -complications related to COVID-19 up to 28 days of discharge from hospital (visit 4) -Number (percentage) of patients who need to be admitted to the ICU - Number (percentage) of patients needing supplemental oxygen since discharge hospitalization until the day of discharge - Number (percentage) of patients needing ICU admission and mechanical ventilation -Number (percentage) of patients diagnosed with other nosocomial infection -Number (percentage) of patients requiring hospital readmission within 28 days (visit 4) of discharge
Mortality: - Number (percentage) of COVID-19-related deaths up to 28 days from hospital discharge (visit 4) -Number (percentage) of patients who died from any cause up to 28 days after discharge from hospital (visit 4) -Number of days until death safety: -Incidence of adverse events according to their severity and relationship to treatment -Number of patients with a grade 3 or 4 or 5 adverse reaction according to the CTC-EA |
Clínicos: •Número (porcentaje) de pacientes que alcanzan un grado 2 o grado 1 durante los 10 días de haber iniciado el tratamiento. • Número (porcentaje) de pacientes que se le haya dado el alta hospitalaria y que desde el alta hospitalaria hasta el día 28 del alta hospitalaria no presente una recaída o comorbilidad relacionada con COVID-19 •Tiempo (‘días’) hasta alcanzar un estado afebril: temperatura corpórea menor o igual de37,5ºC durante 48 horas seguidas sin medicación antipirética •Eficacia a largo plazo (hasta 28 días del alta hospitalaria, visita 4): “número de pacientes” que en el día 28 del alta hospitalaria continúan en grado 2 o grado 1 de la escala ordinal del estado clínico del paciente desde el alta hospitalaria. •Número de días de estancia hospitalaria (desde el día del inicio del tratamiento antiviral hasta elalta hospitalaria)complicaciones relacionadas con COVID-19 hasta los 28 días del alta hospitalaria (visita 4): •Número (porcentaje) de pacientes que necesitan ingresar en la UCI • Número (porcentaje) de pacientes que necesitan oxígeno suplementario desde el alta hospitalaria hasta el día del alta • Número (porcentaje) de pacientes que necesitan ingresar en la UCI y ventilación mecánica •Número (porcentaje) de pacientes a los que se diagnostica otra infección nosocomial •Número (porcentaje) de pacientes que necesitan un reingreso hospitalario antes de los 28 días(visita 4) desde el alta hospitalaria
Mortalidad: • Número (porcentaje) de pacientes fallecidos relacionadas con COVID-19 hasta los 28 días del alta hospitalaria (visita 4) •Número (porcentaje) de pacientes fallecidos por cualquier causa hasta los 28 días desde el alta hospitalaria (visita 4) •Número de días hasta deceso SEGURIDAD: •Incidencia de acontecimientos adversos según su gravedad y relación con el tratamiento •Número de pacientes con una reacción adversa de grado 3 ó 4 ó 5 según los CTC-AE. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the study. |
Durante todo el estudio. |
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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 | 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 | 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 |
Tratamiento estándar de cuidado |
Standard of care treatment |
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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
| 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 | 5 |
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
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LVLP (last visit last patient) |
Última visita del último paciente. |
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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 | 18 |
E.8.9.1 | In the Member State concerned days | |