E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Catecholamine-resistant hypotension associated with distributive shock |
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E.1.1.1 | Medical condition in easily understood language |
Low blood pressure that is resistant to correction by treatment with catecholamines |
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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) |
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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 |
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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. |
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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. |
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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 |
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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 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3h, 24h and 48h post baseline |
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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 | 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
| 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 | 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
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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 |