E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Catecholamine-resistant hypotension associated with distributive shock |
Hipotensión resistente a las catecolaminas asociada a shock distributivo |
|
E.1.1.1 | Medical condition in easily understood language |
Low blood pressure that is resistant to correction by treatment with catecholamines |
Presión arterial baja que es resistente a ser corregida con tratamiento a base de catecolaminas |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
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 the effect of LJPC-501 infusion on mean arterial pressure (MAP) as assessed by standard of care vasopressor dose reduction in paediatric patients with catecholamine-resistant hypotension (CRH) |
• Evaluar el efecto de la infusión de LJPC-501 en la presión arterial media (PAM), evaluado mediante la reducción de la dosis de vasopresores de referencia en pacientes pediátricos con hipotensión resistente a las catecolaminas (HRC) |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate change in the Paediatric Logistic Organ Dysfunction-2 (PELOD-2) score • To establish the safety and tolerability of LJPC-501 in paediatric patients with CRH • To evaluate changes in catecholamine and other vasopressor doses over time • To evaluate the change in MAP over time |
• Evaluar el cambio en la puntuación PELOD-2 (Paediatric Logistic Organ Dysfunction-2) • Establecer la seguridad y la tolerabilidad de LJPC-501 en pacientes pediátricos con HRC • Evaluar los cambios en la dosis de catecolaminas y otros vasopresores a lo largo del tiempo • Evaluar el cambio de la PAM a lo largo del tiempo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: 1. Paediatric patients > 2 years (ie, > 24 months) to < 18 years of age at enrolment. 2. Patients requiring a sum norepinephrine-equivalent dose > 0.1 μg/kg/min to maintain ageappropriate target MAP for a minimum of 2 hours and a maximum of 48 hours prior to initiation of study drug. 3. Patients must have a clinical diagnosis of distributive shock in the opinion of the treating team and the Investigator. 4. Patients are required to have central venous access, which is expected to remain present for the duration of study drug treatment. 5. Patients are required to have an indwelling arterial line, which is expected to remain present for at least the first 48 hours of study drug treatment. 6. Patients must have received at least 40 mL/kg of crystalloid or colloid equivalent over the initial 24-hour resuscitation period, and must be adequately volume resuscitated in the opinion of the Investigator, prior to starting study drug. 7. Parent(s) or legal guardian(s) is willing and able to provide informed consent and assist the patient in complying with all protocol requirements. |
1. Pacientes pediátricos de >2 años (es decir, >24 meses) a <18 años de edad en el momento de la inscripción. 2. Pacientes que necesiten una dosis total de equivalentes de norepinefrina >0,1 μg/kg/min para mantener la PAM deseada adecuada para la edad durante un mínimo de 2 horas y un máximo de 48 horas antes de comenzar el tratamiento con el medicamento del estudio. 3. Los pacientes deben tener un diagnóstico clínico de shock distributivo en opinión del equipo responsable del tratamiento y del investigador. 4. Los pacientes deben llevar una vía venosa central, que se espera que permanezca colocada durante todo el tratamiento con el medicamento del estudio. 5. Los pacientes deben llevar una vía arterial permanente, que se espera que permanezca colocada durante al menos las primeras 48 horas del tratamiento con el medicamento del estudio. 6. Los pacientes deben haber recibido por lo menos 40 ml/kg de un cristaloide o un equivalente a un coloide durante el período de reanimación de 24 horas inicial, y se debe haber conseguido una reposición de la volemia adecuada en opinión del investigador antes de comenzar el tratamiento con el medicamento del estudio. 7. El/Los progenitor/es o tutor/es legal/es está dispuesto y es capaz de proporcionar el consentimiento informado y ayudar al paciente a cumplir con todos los requisitos del protocolo. |
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E.4 | Principal exclusion criteria |
Exclusion criteria: 1. Patients who are <=2 years (24 months) of age or >= 18 years of age at enrolment. 2. Patients with a standing Do Not Resuscitate order. 3. Patients diagnosed with acute occlusive coronary syndrome requiring pending intervention. 4. Patients on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO). 5. Patients who have been on veno-venous (VV) ECMO for less than 6 hours. 6. Patients with a clinical suspicion of cardiogenic shock based on echocardiogram. 7. Patients who have a history of asthma or are currently experiencing bronchospasm requiring the use of inhaled bronchodilators and who are not mechanically ventilated. 8. Patients with acute mesenteric ischaemia or a history of mesenteric ischaemia. 9. Patients with active bleeding AND an anticipated need of multiple transfusions (within 48 hours of Screening). 10. Patients with active bleeding AND haemoglobin < 7 g/dL. 11. Patients with an expected lifespan of < 12 hours or expected withdrawal of life support within 24 hours of Screening. 12. Patients with a known allergy to mannitol. 13. Patients who are currently participating in another clinical trial using an investigational drug not approved in that member country unless specifically approved by the Sponsor. 14. Patients of childbearing potential who are known to be pregnant at the time of Screening. |
1. Pacientes que tengan <=2 años (24 meses) de edad o >=18 años de edad en el momento de la inscripción. 2. Pacientes con una orden vigente de no reanimar. 3. Pacientes con diagnóstico de síndrome coronario oclusivo agudo que requiera una intervención pendiente. 4. Pacientes que estén recibiendo oxigenación por membrana extracorpórea (OMEC) venoarterial (VA). 5. Pacientes que hayan recibido OMEC venovenosa (VV) durante menos de 6 horas. 6. Pacientes con sospecha clínica de shock cardiogénico según el ecocardiograma. 7. Pacientes que tengan antecedentes de asma o que actualmente presenten broncoespasmo que requiere el uso de broncodilatadores inhalados y que no reciban ventilación mecánica. 8. Pacientes con isquemia mesentérica aguda o antecedentes de isquemia mesentérica. 9. Pacientes con hemorragia activa Y una necesidad prevista de múltiples transfusiones (en las 48 horas anteriores a la selección). 10. Pacientes con hemorragia activa Y hemoglobina <7 g/dl. 11. Pacientes con una esperanza de vida prevista <12 horas o una retirada prevista del soporte vital en las 24 horas anteriores a la selección. 12. Pacientes con alergia conocida al manitol. 13. Pacientes que estén participando actualmente en otro ensayo clínico con un medicamento en fase de investigación que no esté aprobado en ese país miembro, a menos que el promotor lo apruebe específicamente. 14. Pacientes con capacidad de procrear que se sepa que están embarazadas en el momento de la selección. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of patients who have achieved >= 50% reduction in vasopressor dose as measured by NED from baseline to Hour 3 |
• Proporción de pacientes a los que se ha podido reducir la dosis de vasopresor >=50 %, medida mediante el cambio de la DEN desde el momento basal hasta la hora 3 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• 3h post baseline |
Desde el momento basal hasta la hora 3 |
|
E.5.2 | Secondary end point(s) |
• Change in PELOD-2 score from baseline to Hour 24 and Hour 48 • Change in catecholamine and other vasopressor doses from baseline to Hour 24 and Hour 48 • Change in MAP from baseline to Hour 3, Hour 24, and Hour 48 • Change in heart rate from baseline to Hour 3, Hour 24, and Hour 48 |
• Cambio en la puntuación PELOD-2 entre el momento basal y las horas 24 y 48 • Cambio en la dosis de catecolaminas y otros vasopresores entre el momento basal y las horas 24 y 48 • Cambio en la PAM entre el momento basal y las horas 3, 24 y 48 • Cambio en la frecuencia cardíaca entre el momento basal y las horas 3, 24 y 48 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
3h, 24h and 48h post baseline |
Entre el momento basal y las horas 3, 24 y 48 |
|
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 | No |
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 | 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 | 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 | 39 |
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
|
LPLV |
Última visita de ultimo 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 | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |