E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Evaluation of the effectiveness of antimicrobial prophylaxis in infants with vesico-ureteral reflux grade III-V, started before the first symptomatic infection |
Evaluación de la efectividad de la profilaxis antimicrobiana en niños con RVU grado III-V, antes de la primera infección sintomática. |
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E.1.1.1 | Medical condition in easily understood language |
Evaluation of the effectiveness of antimicrobial prophylaxis in infants with vesico-ureteral reflux grade III-V, started before the first symptomatic infection |
Evaluación de la efectividad de la profilaxis antimicrobiana en niños con RVU grado III-V, antes de la primera infección sintomática. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047371 |
E.1.2 | Term | Vesicoureteral reflux |
E.1.2 | System Organ Class | 100000004857 |
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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 |
The primary objective is the evaluation of the effectiveness of antimicrobial prophylaxis in infants with vesico-ureteral reflux grade III-V, started before the first symptomatic infection. |
El objetivo principal es la evaluación de la efectividad de la profilaxis antimicrobiana en niños con RVU grado III-V, antes de la primera infección sintomática. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are the evaluation of 1. the role of symptomatic and febrile UTIs on the appearance and progression of kidney damage and development of renal function; 2. the natural history of renal function of paediatric patients with congenital kidney or urinary tract anomalies during the first 5 years of life; 3. the natural evolution of vesico-ureteral reflux during the first 5 years of life and its correlation with UTIs, renal scars and impairment of renal function; 4. the hypothetic role of prophylactic antibiotic therapy during the first months of life on BMI at 2 and 5 years of age. |
Los objetivos secundarios son la evaluación de: 1. El papel de Ias ITUs sintomáticas y febriles, en la aparición y progresión del daño renal y el desarrollo de la función renal; 2. La historia natural de la función renal de los pacientes pediátricos con enfermedad renal congénita o anomalías del tracto urinario durante los primeros 5 años de vida; 3. La evolución natural del RVU durante los primeros 5 años de vida y su relación con las ITUs, las cicatrices y las alteraciones de la función renal; 4. El papel hipotético de la terapia antibiótica profiláctica durante los primeros meses de vida en el IMC de los 2 y 5 años de edad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Age between 1 and 4 months b. Gestational age > 35 weeks c. Glomerular filtration rate (calculated according to Schwartz) > 15 ml/min/1.73 m2 at three months of age d. No previous symptomatic UTI e. Imaging Diagnostic work-up completed and presence of grade III to V vesico-ureteral reflux f. Informed consent of parents |
a. Edad entre 1 y 4 meses b. Edad gestacional > 35 semanas c. Tasa de filtración glomerular (calculado de acuerdo con Schwartz) > 15 ml/min/1,73 m2 a los tres meses de edad d. Sin previas ITUs sintomáticas e. Diagnóstico por imagen completo y presencia de reflujo vesico-ureteral de grado III a V f. Consentimiento informado firmado por los padres |
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E.4 | Principal exclusion criteria |
a. Age <1 and >4 months b. Gestational age < 35 weeks c. Glomerular filtration rate (calculated according to Schwartz) < 15 ml/min/1.73 m2 at three months of age d. Patients with neurogenic bladder, myelomeningocele, uretero-pelvic junction and/or uretero-vescico junction obstruction, or other malformations leading to potential voiding disturbances, apart from urethral valves e. Patients with no or low grade reflux (grade I and II). f. Hypersensitivity to the all the utilized antimicrobial agent g. Children with serious clinical conditions which, according to the investigator, prevent them from being included in the study cohort. h. Use of experimental drugs in the month previous to the beginning of the study i. Children unable to follow the established protocol procedures or whose parents are unable to sign the informed consent. |
a. Edad <1 y> 4 meses b. Edad gestacional <35 semanas c. Tasa de filtración glomerular (calculado de acuerdo con Schwartz) <15 ml/min/1,73 m2 a los tres meses de edad d. Pacientes con vejiga neurogénica, mielomeningocele, unión uretero-pélvica y/o obstrucción de la unión uretero-vescical, u otras malformaciones que conducen a posibles alteraciones miccionales, aparte de las válvulas uretrales e. Pacientes sin o con bajo grado de reflujo (grado I y II) f. Hipersensibilidad a todo agente antimicrobiano utilizado g. Niños con situaciones clínicas graves que, de acuerdo con el investigador, deben evitar ser incluidos en la cohorte del estudio h. El uso de medicamentos experimentales en el mes anterior al inicio del estudio i. Niños que no puedan seguir los procedimientos del protocolo establecidos o cuyos padres no pueden firmar el consentimiento informado |
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E.5 End points |
E.5.1 | Primary end point(s) |
Symptomatic urinary tract infection rate during the 24-month observation period. |
Tasa de la primera infección urinaria sintomática durante el período de observación de 24 meses. |
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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) |
Number of febrile UTIs and of new renal scars (DMSA scan) at the 2 and 5 years follow-up in relation to the development of renal function (creatinine and Cystatin C plasma values, eGFR), hypertension (blood pressure >95th%ile per age, sex and height) and/or proteinuria (protein/creatinine), anatomical growth (renal length) of the kidneys at 2 and 5 years follow-up, evaluation of the natural course of renal function for hypo-dysplastic kidneys during the first 5 years of life |
ITU febril, el número de nuevas cicatrices renales a los 2 y 5 años; el desarrollo de la función renal, la hipertensión y/o proteinuria, el crecimiento anatómico de los riñones a los 2 y 5 años de seguimiento, la evaluación del curso natural de la función renal de los riñones hipodisplásicos durante los primeros 5 años de vida y la evaluación del IMC en 2 y 5 años de edad. |
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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 | 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) | 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 |
Vigilancia clínica habitual |
NO drug, normal clinical surveillance |
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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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Belgium |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Lithuania |
Poland |
Portugal |
Serbia |
Spain |
Switzerland |
Turkey |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |