| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| complicated bacterial skin and soft tissue infections |
| infecciones bacterianas complicadas de la piel y tejidos blandos |
|
| E.1.1.1 | Medical condition in easily understood language |
| skin infections |
| infecciones de la piel |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10021881 |
| E.1.2 | Term | Infections and infestations |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 whether ceftaroline fosamil is noninferior to vancomycin plus aztreonam in the clinical cure rate at the test of cure visit in both the modified intent-to-treat and clinically evaluable anlaysis sets of adult patients with complicated skin and soft tissue infections (cSSTI) |
| El objetivo principal es evaluar si la ceftarolina fosamilo no es inferior a vancomicina más aztreonam en la tasa de curación clínica en la visita de comprobación de curación (CDC) tanto en el grupo de análisis de pacientes adultos con IPTBc basado en la intención de tratar modificada (ITM) como en el de pacientes adultos con IPTBc evaluables desde el punto de vista clínico (EC). |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the clinical response at the End of Therapy Visit.
To evaluate the microbiological response at the End of Therapy and Test of Cure Visits
To evaluate the clinical and microbiological response by baseline pathogen at the Test of Cure Visit
To evaluate clinical relapse and re-infection or recurrence at the Late Follow-Up (LFU) visit
To evaluate superinfection, colonisation and new infection up to TOC and microbiological recurrence and re-infection at LFU
To evaluate early response to treatment as defined by cessation of lesion spread at 48 to 72 hours of treatment
To compare the safety and tolerability of ceftaroline fosamil and vancomycin plus aztreonam in patients with cSSTI
To characterize the pharmacokinetics (PK) and exposure-response relationship of 600 mg of ceftaroline fosamil administered as a 120-minute intravenous (IV) infusion every 8 hours in patients with cSSTI |
- Evaluar la respuesta clínica en la visita de final del tratamiento (FDT)
- Evaluar la respuesta microbiológica en las visitas FDT y CDC
- Evaluar la respuesta clínica y microbiológica por patógeno basal en la visita CDC
- Evaluar la recidiva clínica y la reinfección o la recidiva en la visita de seguimiento tardío (ST)
- Evaluar la sobreinfección, la colonización y las nuevas infecciones hasta la visita CDC, y la recidiva microbiológica y la reinfección en la visita ST
- Evaluar la respuesta precoz al tratamiento definida por el cese de la diseminación de las lesiones a las 48-72 horas de tratamiento
- Comparar la seguridad y la tolerabilidad de ceftarolina fosamilo y vancomicina más aztreonam en pacientes con IPTBc
- Caracterizar la farmacocinética (FC) y la relación entre exposición y respuesta de 600 mg de ceftarolina fosamilo administrada como infusión intravenosa (IV) de 120 minutos cada 8 horas en pacientes con IPTBc |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient must provide a signed written informed consent prior to any study-specific procedures
2. Patient must be a male or female, aged 18 years and older
3. Patient must have one of the following cSSTIs:
- Cellulitis: a diffuse skin infection characterised by spreading areas of erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, minimum length of 10 cm and width of 7.5 cm)
- Traumatic or surgical wound infection: an infection characterised by purulent drainage/or collection from an injury-related wound or a surgical wound with surrounding erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, the shortest distance of redness, oedema, and/or induration extending at least 5 cm from the peripheral margin of the wound). Appropriate surgical intervention must be completed prior to the first dose of study drug or up to, at most, 48 hours after the first dose of study drug.
- Major cutaneous abscess: an infection characterised by a collection of pus within the dermis or deeper that is accompanied by erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, the shortest distance of redness, oedema, and/or induration extending at least 5 cm from the peripheral margin of the abscess). The abscess must undergo incision and drainage prior to the first dose of study drug or up to, at most, 48 hours after the first dose of study drug. The number of patients with major cutaneous abscesses will be limited to no more than30% of the study population.
- Burn infection: an infection characterised by purulent drainage, erythema, oedema, and/or induration of a minimum surface area of 75 cm2 (eg, the shortest distance of redness, oedema, and/or induration extending at least 5 cm from the peripheral margin of the burn infection). Burns must involve less than 15% of the body surface area and acquired within 7 days of hospitalisation. Appropriate surgical intervention must be completed prior to the first dose of study drug or up to, at most, 48 hours after the first dose of study drug.
4. Patients must demonstrate at least one of the following criteria (for the first 3 bullets, the criterion must be met within 24 hours prior to first dose of study drug):
- Temperature >= 38.0°C (100.4°F) or <= 36.0°C (96.8°F)
and/or
- White blood cells >12000 cells/mm3 or <4000 cells/mm3 or >10% band forms
(immature white blood cells)
and/or
- Heart rate >90 beats per minute and respiratory rate >20 breaths per minute after
10 minutes of rest
and/or
- One or more of the following comorbidities:
- Diabetes mellitus requiring drug therapy (note: patients with diabetic foot infections are excluded as per exclusion criterion #8)
- Stage 2 or 3 HIV infection (per Center for Disease control classification 2008) (note: patients with a CD4 count <150 cell/microliter within 6 months prior to first dose of study drug or suspected opportunistic infection are excluded)
- Chronic renal impairment (estimated creatinine clearance >= 20 mL/min to <50 mL/min) as calculated by the Cockcroft-Gault formula
- Cirrhosis with Child-Pugh Stage A or B (note: patients with Child-Pugh
Stage C are excluded)
- cSSTI below the knee associated with peripheral vascular disease diagnosed on the basis of any of the following: claudication at a distance of at least 20 meters; resting ankle-brachial index 0.3 to 0.8; prior femoral artery bypass grafting; or prior aortic aneurysm repair (note: patients with ulcers due to peripheral vascular disease are also excluded)
- Albumin <2.5 mg/dL or prealbumin <11 mg/dL in the absence of liver disease
- Use of immunosuppressive agents, including a glucocorticoid (Note: patient who is receiving or has received >40 mg per day of prednisone or equivalent for more than 1 week within the 2 weeks prior to study enrolment is excluded)
- Malignancy, other than nonmelanoma skin cancers, with a life expectancy of >3 months
5. Patient must have an infection of sufficient severity to warrant hospitalisation
6. Patient must have an infection of sufficient severity such that it is expected to require at least 5 days of IV antibiotic therapy
7. Female patients of childbearing potential may be entered if pregnancy testing is negative and the patient agrees to abstain from procreational sexual intercourse or must use double-barrier contraceptive measures for the duration of the study |
1. El paciente deberá otorgar un consentimiento informado por escrito firmado antes de realizar ningún procedimiento específico del estudio.
2. Los pacientes deben ser varones o mujeres mayores de 18 años.
3. Los pacientes deben presentar alguna de las siguientes IPTBc:
- Celulitis
- Infección de herida quirúrgica o traumática.
- Absceso cutáneo grave.
- Infección de quemaduras.
4. Los pacientes deben mostrar al menos uno de los criterios siguientes (en los tres primeros puntos, el criterio deberá cumplirse en las 24 horas previas a la primera dosis del fármaco del estudio):
- Temperatura >= 38,0 ºC o <= 36,0 ºC
y/o
- Recuento leucocitario >12.000 células/mm3 o <4.000 células/mm3 o >10 % de cayados (leucocitos inmaduros)
y/o
- Frecuencia cardíaca >90 latidos por minuto y frecuencia respiratoria >20 respiraciones por minuto después de 10 minutos de reposo
y/o
- Una o más de las siguientes enfermedades concomitantes:
- Diabetes mellitus que requiera farmacoterapia (nota: los pacientes con infecciones del pie diabético están excluidos conforme al criterio de exclusión n.º 8).
- Infección por VIH en estadio 2 ó 3 (conforme a la clasificación de 2008 de los Centers for Disease Control) (Schneider y cols., 2008) (nota: están excluidos los pacientes con recuento de CD4 <150 células/microlitro durante los 6 meses previos a la primera dosis del fármaco del estudio o que se sospeche que padezcan infecciones oportunistas).
- Insuficiencia renal crónica (aclaramiento de creatinina estimado comprendido >= 20 ml/min y <50 ml/min) calculada mediante la fórmula de Cockcroft Gault (Cockcroft y cols., 1976) incluida en el Apéndice D.
- Cirrosis en estadio A o B de Child Pugh (nota: se excluye a los pacientes con cirrosis en estadio C de Child Pugh)
- IPTBc por debajo de la rodilla asociada a vasculopatía periférica diagnosticada basándose en cualquiera de los siguientes criterios: claudicación a una distancia de al menos 20 metros; índice tobillo brazo de 0,3 a 0,8 en reposo; injerto de derivación de arteria femoral previo; o reparación previa de aneurisma aórtico (nota: los pacientes con úlceras debidas a vasculopatía periférica también están excluidos).
- Albúmina <2,5 mg/dl o prealbúmina <11 mg/dl en ausencia de hepatopatía.
- Uso de agentes inmunosupresores, como los glucocorticoides (nota: se excluye a los pacientes que reciben o han recibido >40 mg al día de prednisona o equivalente durante más de una semana durante las dos semanas previas a la inclusión en el estudio).
- Neoplasia maligna, excepto los cánceres de piel distintos del melanoma, con una esperanza de vida >3 meses.
5. Los pacientes deben tener una infección de intensidad suficiente como para que requiera hospitalización.
6. Los pacientes deben tener una infección de intensidad suficiente como para sea previsible que requiera al menos 5 días de antibioterapia IV.
7. Las mujeres en edad fértil podrán participar si la prueba de embarazo es negativa y la paciente accede a no mantener relaciones sexuales procreativas o deberá utilizar métodos anticonceptivos de doble barrera durante el estudio. |
|
| E.4 | Principal exclusion criteria |
. Received systemic antibacterial drugs for greater than 24 hours within 96 hours prior to first dose of study drug
. Uncomplicated skin and skin structure infections, skin infections suspected to be caused by viral or fungal pathogens
. Diabetes, diabetic foot infections, decubitus ulcers, ulcers due to peripheral vascular disease
. Infection caused by human or animal bites, sternal wound infections, bone infection or arthritis due to an infection, critical limb ischemia of the affected limb
. Chronic liver disease or severe impaired renal function, severe low white blood cell count, burns on greater than 15% of total body surface area, necrotizing skin infection, amputation required of primary site of infection, sustained shock |
El paciente ha recibido antibacterianos sistémicos durante >24 horas en las 96 horas previas a la primera dosis del fármaco del estudio.
El paciente tiene infecciones no complicadas de la piel y de las estructuras cutáneas, que se sospecha que está causada por patógenos víricos o fúngicos.
Diabetes, infecciones de pie por diabetes, úlceras de decúbito, úlceras debidas a enfermedad vascular periférica.
Infección causada por mordeduras humanas o animales, infecciones de heridas externas, infección ósea o artritis debida a una infección, isquemia grave de la extremidad afectada.
Enfermedad hepática crónica o insuficiencia renal grave, recuento de leucocitos bajo y grave, quemaduras en más del 15% de la superficie corporal total, infección cutánea necrosante, amputación necesaria de la parte principal de la infección, shock sostenido. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To assess the clinical cure rate in both the modified intent-to-treat and clinically evaluable analysis sets |
| Evaluar la tasa de curación clínica en la visita en los grupos de análisis de intención de tratar y evaluable desde el punto de vista clínico. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| at the test of cure visit |
| en el análisis de la visita de curación |
|
| E.5.2 | Secondary end point(s) |
1. To assess the clinical cure rate in the modified intent-to-treat and clinically evaluable analysis sets
2. To assess the per-patient microbiological response in the microbiological modified intent-to-treat and microbiologically evaluable analysis sets
3. To assess the clinical and per-pathogen microbiological response by baseline pathogen in the microbiological modified intent-to-treat and microbiologically evaluable analysis sets
4. To assess clinical relapse in patients who were clinically cured at the test of cure visit in the clinically evaluable analysis set
5. To assess re-infection and recurrence rate in patients who were microbiological successes at the test of cure visits in the microbiologically evaluable analysis set
6. To assess super-infection rate in the microbiologically evaluable anlaysis set
7. To assess new infection rate in the microbiologically evaluable analysis set
8. To assess colonization rate in patients who had a clinical assessment in the microbiologically evaluable analysis set
9. To assess the evaluation of early response in the modified intent-to-treat and clinically evaluable anlaysis sets
10. To assess the safety and tolerability by incidence and severity of adverse events, vital signs, clinical laboratory tests, ECGs and physicial exam |
Evaluación de:
1- Tasa de curación clínica en los grupos de análisis ITM y EC.
2- Respuesta microbiológica por paciente en los grupos de análisis ITMm y EM.
3- Respuesta microbiológica clínica y por patógeno en función del patógeno basal en los grupos de análisis ITMm y EM.
4- Recidiva clínica en pacientes que presenten curación clínica en la visita CDC en el grupo de análisis EC.
5- Tasa de reinfección y de recidiva en pacientes con curación microbiológica en la visita CDC en el grupo de análisis EM.
6- Tasa de sobreinfección en el grupo de análisis evaluable microbiológicamente.
7- Tasa de nueva infección en el grupo de análisis evaluable microbiológicamente.
8- Tasa de colonización en pacientes con evaluación clínica realizada en el grupo de análisis evaluable microbiológicamente.
9- La respuesta precoz en los grupos de análisis ITM y EC.
10- La seguridad y la tolerabilidad se evaluarán mediante la incidencia y la intensidad de los acontecimientos adversos (AA), de las constantes vitales, las evaluaciones analíticas, los ECGs y las exploraciones físicas. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at the end of therapy visit
2. at the end of therapy and test of cure visits
3. at the test of cure visit
4. at the late follow-up visit
5. at the late follow up visit
6. at the end of therapy visit
7. at the test of cure visit
8. at the end of therapy visit or the test of cure visit
9. at 48 to 72 hours of treatment
10. study duration |
1. al final de la visita de tratamiento
2. al final del tratamiento y en el análisis de la visita de curación
3. en el análisis de las visitas de curación
4. en la visita de seguimiento tardía
5. en la visita de seguimiento tardía
6. al final de la visita de tratamiento
7. en el análisis de la visita de curación
8. al final de la visita de tratamiento o en el análisis de la visita de curación
9. a las 48 - 72 horas del tratamiento
10. duración del estudio |
|
| 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 | Yes |
| 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 81 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Australia |
| Austria |
| Belgium |
| Brazil |
| Bulgaria |
| Chile |
| Colombia |
| Croatia |
| Czech Republic |
| France |
| Germany |
| Greece |
| Hong Kong |
| Israel |
| Italy |
| Korea, Republic of |
| Mexico |
| Netherlands |
| Peru |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| Slovakia |
| South Africa |
| Spain |
| Switzerland |
| Taiwan |
| Thailand |
| Turkey |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
| LSLV |
| Última visita, último paciente |
|
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
