A controlled multicenter study to assess efficacy and safety of LJPC-501 in children > 2 to 17 years of age with severely low blood pressure associated with shock

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2017-005153-37-EE
• Date of registration: 18/04/2018
• Prospective Registration: Yes
• Primary sponsor: La Jolla Pharmaceutical Company
• Public title: A controlled multicenter study to assess efficacy and safety of LJPC-501 in children > 2 to 17 years of age with severely low blood pressure associated with shock
• Scientific title: A Randomised, Placebo-controlled, Double-blind, Multicentre Efficacy and Safety Study of LJPC-501 in Paediatric Patients > 2 to 17 Years of Age with Catecholamine-Resistant Hypotension Associated with Distributive Shock
• Date of first enrolment: 21/06/2018
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-005153-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Estonia, France, Lithuania, Spain, United Kingdom

Contacts

• Name: Rena Harrigan
• Affiliation: La Jolla Pharmaceutical Company

• Name: Rena Harrigan
• Affiliation: La Jolla Pharmaceutical Company

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Catecholamine-resistant hypotension associated with distributive shock

Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

Intervention(s)

Product Name: GiaprezaTM
Product Code: LJPC-501
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Angiotensin II acetate
Current Sponsor code: LJPC-501
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: • 3h post baseline

Primary end point(s): • Proportion of patients who have achieved = 50% reduction in vasopressor dose as measured by NED from baseline to Hour 3

Secondary Objective: • 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

Main Objective: • 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)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 3h, 24h and 48h post baseline

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

Secondary ID(s)

LJ501-CRH04

2017-005153-37-BE

Source(s) of Monetary Support

La Jolla Pharmaceutical Company

Ethics review

Status: Approved
Approval date:
Contact: