E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric Hypertension With or Without CKD |
Hipertensión pediátrica con o sin enfermedad renal crónica (ERC) |
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E.1.1.1 | Medical condition in easily understood language |
High blood pressure in paediatrics with or without chronic kidney disease |
Presión arterial alta en pacientes pediátricos, con o sin enfermedad renal crónica |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 evaluate if a dose dependent reduction in MSBP exists when comparing two doses of valsartan solution over a 6wk period in children 1-5 years old with hypertension with or without CKD. |
Evaluar si existe una reducción proporcional a la dosis de la PASM al comparar dos dosis de valsartán en solución durante un periodo de 6 semanas en niños de 1-5 años con hipertensión, con o sin ERC. |
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E.2.2 | Secondary objectives of the trial |
Assess efficacy of valsartan in reducing MDBP; assess efficacy of valsartan in controlling MSBP and MDBP; to assess safety and toleribilty profile; assess proteinuria and eGFR |
Evaluar la eficacia del valsartán para reducir la PADM; evaluar la eficacia del valsartán para controlar la PASM y la PADM; evaluar el perfil de seguridad y tolerabilidad; evaluar la proteinuria y la FGe. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria: - Have the ability to provide written informed consent; - Have at baseline , a documented diagnosis of hypertension (as defined in the National High Blood Pressure Education Program 2004); - MSBP (mean of 3 measurements) must be >= 95th percentile, and <=25% above the 95th percentile, for age, gender and height, at baseline; - CKD patients must be defined as any of the following criteria: 1. Kidney damage for >= 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by one or more of the following features: - Abnormalities in the composition of urine - Abnormalities in imaging tests - Abnormalities on kidney biopsy 2. Estimated eGFR <60 mL/min/1.73m2 (calculated by Modified Schwartz Formula) for >= 3 months, with or without the other signs of kidney damage described above. - Able to swallow the valsartan solution; Body weight must be >=8 kg and <=40 kg at baseline; - Must be able to safely washout from other antihypertensive therapy (if applicable) |
Podrán participar en el estudio los pacientes que cumplan todos los criterios siguientes: - Capacidad de proporcionar consentimiento informado por escrito; - Tener un diagnóstico documentado de hipertensión en el momento basal (según el National High Blood Pressure Education Program 2004); - PASM (media de tres determinaciones) >= percentil 95 y <=25% por encima del percentil 95 para la edad, el sexo y la talla en el momento basal; - Los pacientes con ERC deberán cumplir alguno de los siguientes criterios: 1. Lesión renal durante >= 3 meses, definida como anomalías estructurales o funcionales del riñón, con o sin reducción de la FG, que se manifiesta por medio de una o más de las siguientes características: - Anomalías en la composición de la orina - Anomalías en las pruebas de imagen - Anomalías en la biopsia renal 2. FG estimada <60ml/min/1,73 m2 (calculada mediante la Fórmula de Schwartz modificada) durante >= 3 meses, con o sin los otros signos de lesión renal descritos anteriormente. - Capacidad de tragar la solución de valsartán; Peso corporal >= 8 Kg y <= 40 Kg en el momento basal; - Capacidad de someterse con seguridad a un lavado del tratamiento con otros antihipertensivos (si procede). |
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E.4 | Principal exclusion criteria |
- Aspartate Aminotransferase / Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) or Alanine Aminotransferase/Serum Glutamic Pyruvic Transaminases (ALT/SGPT) >3 times the upper limit of the reference range; - Estimated Glomerular Filtration Rate [eGFR] <30 mL/min/1.73m² (calculated using Modified Schwartz Formula); Serum potassium >5.3 mmol/L; - Uncontrolled diabetes mellitus, as defined by the investigator; - Unilateral, bilateral and graft renal artery stenosis; - Current diagnosis of heart failure (NYHA Class II-IV); - Patients taking any of the following concomitant medications following screening: RAAS blockers other than study drug, Lithium, Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels; - Non-steroidal anti-inflammatory drugs (NSAIDS), including selective COX-2 inhibitors, acetylsalicylic acid >3g/day, and non-selective NSAIDs (paracetamol/acetaminophen is permitted); - Antidepressant drugs in the class of MAO inhibitors (e.g. phenelzine); Chronic use of stimulant therapy for ADD/ADHD; - patients who have coarctation of the aorta with a gradient of >=30 mmHg; - Previous solid organ transplantation except renal transplantation. Renal transplant must have occurred at least 1 year prior to enrollment; - Patient must be on stable doses of immunosuppressive therapy and deemed clinically stable by the investigator; - Patients known to be positive for the human immunodeficiency virus (HIV) Other protocol defined inclusion/exclusion criteria may apply. |
- Aspartato Aminotransferasa/Transaminasa glutámico-oxaloacética sérica (AST/SGOT) o Alanina Aminotransferasa/ Transaminasa glutámico-pirúvica sérica (ALT/SGPT) > 3 veces el límite superior del intervalo de referencia; - Filtración glomerular estimada (FGe) <30 ml/min/1,73 m2 (calculada mediante la fórmula de Schwartz modificada); Potasio sérico > 5,3 mmol/l; - Diabetes mellitus no controlada, definida por el investigador; - Estenosis de arteria renal unilateral, bilateral o de injerto; - Diagnóstico presente de insuficiencia cardíaca (clase II-IV de la NYHA); - Pacientes en tratamiento concomitante con cualquiera de los medicamentos siguientes después de la selección: Antagonistas del SRAA distintos del fármaco del estudio; Litio; diuréticos ahorradores de potasio, suplementos de potasio, sustitutos de la sal que contengan potasio y otras sustancias que puedan incrementar las concentraciones de potasio; Antiinflamatorios no esteroideos (AINE), incluidos inhibidores selectivos de la COX 2, ácido acetilsalicílico en una dosis > 3 g/día y AINE no selectivos (se permite el uso de paracetamol); Antidepresivos del grupo de los inhibidores de la MAO (por ejemplo, fenelzina); Uso crónico de tratamiento estimulante por TDA/TDAH. - Pacientes con coartación de la aorta con un gradiente >= 30 mm Hg. - Trasplante de órgano sólido previo, excepto trasplante renal. El trasplante renal deberá haberse practicado al menos un año antes de la inclusión. El paciente deberá estar recibiendo dosis estables de tratamiento inmunosupresor y ser considerado clínicamente estable por parte del investigador; - Pacientes seropositivos para el virus de la inmunodeficiencia humana (VIH) También aplican otros criterios de inclusión/exclusión definidos en el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline (Week 0) in mean systolic blood pressure (MSBP) at Week 6 endpoint [ Time Frame: Baseline, week 6 ] [ Designated as safety issue: No ] Patient's blood pressure will be measured in the same position at every visit. Systolic and diastolic blood pressures will be measured three times at 2-3 minute intervals. The arithmetic mean of these three blood pressure measurements will be used as the mean office blood pressure (MSBP and MDBP) for that visit. |
Variación de la presión arterial sistólica media (PASM) entre el momento basal (semana 0) y la semana 6 . La presión arterial del paciente se medirá en la misma posición en todas las visitas. Las presiones arteriales sistólica y diastólica se medirán tres veces a intervalos de 2-3 minutos. La media aritmética de estas tres determinaciones de presión arterial se utilizará como presión arterial media en el consultorio (PASM y PADM) en esa visita. |
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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) |
Change from baseline in mean diastolic blood pressure (MDBP) at Week 6 and end of study (26 weeks) Percentage of patients achieving MSBP < 90th percentile for age, gender and height at Week 6 endpoint and end of study (26 weeks) Number of patients with Urine Albumin Creatinine Ratio (UACR) response at Week 6 endpoint and end of study (26 weeks) Number of patients with adverse events, serious adverse events and death |
Variación de la presión arterial diastólica media (PADM) entre el momento basal y la semana 6 y el final del estudio (26 semanas) Porcentaje de pacientes que logren una PASM < percentil 90 para la edad, el sexo y la talla en la semana 6 y al final del estudio (26 semanas) Número de pacientes con respuesta del cociente albúmina/creatinina en orina (CACO) en la semana 6 y al final del estudio (26 semanas) Número de pacientes con acontecimientos adversos, acontecimientos adversos graves y muerte. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 6 and 26 |
Semanas 6 y 26 |
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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) | 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 | 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 | Yes |
E.8.2.3 | Other | No |
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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
Brazil |
Germany |
Guatemala |
Hungary |
Lithuania |
Poland |
Spain |
United Kingdom |
United States |
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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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LVLS |
Ultima 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |