A Study of LJPC-501 in Pediatric Patients With Hypotension

Phase 2

Completed

• Conditions: Catecholamine-resistant Hypotension (CRH); Distributive Shock; High Output Shock; Sepsis
• Interventions: Drug: Angiotensin II

• Registration Number: NCT03431077
• Lead Sponsor: La Jolla Pharmaceutical Company

Brief Summary

The objective of this study is to evaluate the effect of LJPC-501 infusion on mean arterial pressure (MAP) or reduction in sum norepinephrine (NE) equivalent dosing, at Hour 2 after the start of LJPC-501, in pediatric patients who remain hypotensive despite receiving fluid therapy and vasopressor therapy. In addition, this study will evaluate the safety and tolerability of LJPC-501 in pediatric patients, the change in MAP over 24 hours after the start of LJPC-501, the change in serum lactate concentrations, and the change in Pediatric Logistic Organ Dysfunction (PELOD) scores.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-18
• Study First Submitted QC: 2018-02-06
• Study Start: 2018-02-11
• Study First Posted: 2018-02-13
• Primary Completion: 2018-04-14
• Study Completion: 2018-04-14
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-06
• Last Update Posted: 2018-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

1. Pediatric patients 2-17 years of age.
2. Patients requiring a total sum NE equivalent dose of > 0.1 μg/kg/min for a minimum of 2 hours and a maximum of 48 hours prior to initiation of LJPC-501 dosing.
3. Patients must have 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 LJPC-501 treatment.
5. Patients are required to have an indwelling arterial line, which is expected to remain present for at least the first 24 hours of LJPC-501 treatment.
6. Patients must have received at least 40 mL/kg of crystalloid or colloid equivalent over the initial 24-hour resuscitation period, and are adequately volume resuscitated in the opinion of the Investigator.
7. Parent or legal guardian is willing and able to provide informed consent and assist the patient in complying with all protocol requirements.

Exclusion Criteria

1. Patients who are < 2 years of age or ≥ 18 years of age.
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.
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 ischemia or a history of mesenteric ischemia.
9. Patients with active bleeding AND an anticipated need of multiple transfusions (within 48 hours of Screening).
10. Patients with active bleeding AND hemoglobin < 7 g/dL or any other condition that would contraindicate serial blood sampling.
11. Patients with an absolute neutrophil count (ANC) of < 500 cells/mm3.
12. Patients requiring more than 5 mg/kg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose.
13. Patients with an expected lifespan of < 12 hours or withdrawal of life support within 24 hours of Screening.
14. Patients with a known allergy to mannitol.
15. Patients who are currently participating in another investigational clinical trial.
16. Patients of childbearing potential who are known to be pregnant at the time of Screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LJPC-501	Angiotensin II	Angiotensin II administered via continuous infusion (1.25 - 40 ng/kg/min) for 24 hours up to 168 hours.

Primary Outcome Measures

Name	Time	Method
Effect of LJPC-501 on mean arterial pressure (MAP)	2 hours	To evaluate the effect of LJPC-501 infusion on mean arterial pressure (MAP).
Effect of LJPC-501 on sum norepinephrine (NE) equivalent dose	2 hours	To evaluate the effect of LJPC-501 in the reduction of the sum norepinephrine (NE) equivalent dosing.

Secondary Outcome Measures

Name	Time	Method
Effect of LJPC-501 on the incidence of treatment-emergent adverse events	Day 7
Effect of LJPC-501 on mean arterial pressure (MAP)	24 hours	To evaluate the change in MAP over 24 hours after the start of LJPC-501.
Effect of LJPC-501 on Pediatric Logistic Organ Dysfunction (PELOD)	24 hours	To evaluate change in Pediatric Logistic Organ Dysfunction (PELOD) score from Screening to 24 hours. The PELOD score is the sum of 6 individual item scores that totals 0-71 points. A higher PELOD score represents a worse outcome.
Effect of LJPC-501 on clinical chemistry laboratory parameters	24 hours	Safety data for clinical chemistry parameters including ALT, AST, ALP, total bilirubin, direct bilirubin, creatinine, BUN, phosphorus, glucose, albumin, calcium, bicarbonate, chloride, sodium, potassium, magnesium, PT, PTT, and INR. In addition, serum pregnancy test will be assessed at screening to confirm eligibility.
Effect of LJPC-501 on hematology laboratory parameters	24 hours	Safety data for laboratory hematology parameters including hemoglobin, hematocrit, platelets, and WBC.
Effect of LJPC-501 on heart rate	Day 7	Change in heart rate (bpm).
Effect of LJPC-501 on body temperature	Hour 24	Change in body temperature (Celsius).
Effect of LJPC-501 on general health	Day 7	Change in physical examination (by body system).
Effect of LJPC-501 on electrical activity of the heart	Hour 24	Change in the electrical activity of the heart over a period of time using electrodes placed on the skin and recorded by electrocardiogram (ECG).
Effect of LJPC-501 on urine output	Day 7	Change in urine output (ml).
Effect of LJPC-501 on serum lactate	2 hours and 24 hours	To evaluate the change in serum lactate concentrations.
Effect of LJPC-501 on blood pressure	Day 7	Change in blood pressure (mmHg).

Trial Locations

Locations (1)

Investigational Site; 🇺🇸 San Antonio, Texas, United States