Efficacy and Safety of Numeta G13%E Compared to Compounded Parenteral Nutrition in Preterm Neonates

Prospective, Multicenter, Open-label, Randomized (1:1 Ratio), Controlled, Parallel Study Comparing Baxter Numeta G13%E to Compounded Parenteral Nutrition (cPN) Solution to Evaluate the Efficacy and Safety of Numeta G13%E in Preterm Neonates

Preterm (PT, born before 37 weeks of gestation) birth complications are the leading causes of death among children aged under 5 years globally, with nearly one million infant deaths reported in 2013. Preterm infants are born with limited nutrient stores, while birth occurs when the nutritional requirements are the highest in human life. Due to the immaturity of their gastrointestinal system, parenteral nutrition (PN) is usually required during the first weeks of life, especially in very low birth weight (VLBW) infants. Despite the availability of national and international guidelines, the initiation of PN is frequently not compliant with current recommendations, especially during the first days of life. In China, like in many other parts of the world, insufficient nutritional supply during hospital stay plays an important role in the postnatal growth restriction (PNGR) of PT infants. Several authors have recently shown that the use of standardized PN formulations can enable optimal early PN intake and can support improved growth rate without adverse consequences in PT infants. Guidelines recommend that standard PN solutions should generally be used over individualized PN solutions in the majority of pediatric and newborn patients, including VLBW infants. They also recommended that individually tailored PN solution should generally be used when the nutritional requirements cannot be met by the available range of standard PN formulations. Given the challenges of optimizing PN practice in PT infants, the aim of this study is to demonstrate non-inferiority of Numeta G13%E to classic compounding practice used for Chinese PT neonates. Please note: Secondary safety endpoints that include Adverse Events (AE) and abnormal blood results will be captured in AE section.

Study Overview

• Status: Withdrawn
• Conditions: Enteral Feeding Intolerance; Malnutrition, Infant
• Intervention / Treatment: Dietary supplement: Numeta G13%E; Dietary supplement: Compounded Parenteral Nutrition (cPN) solution

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• PT birth (>28 and < 37 weeks of gestation)
• Postnatal age < 48 hours
• Medical determination of PN requirement made by the attending physician in conjunction with the Investigator
• An anticipated PN duration after inclusion of at least 5 days
• Requirement for ≥ 80 % of energy intake from PN at inclusion (PN initiation)
• Written ICF signed by the patient's legal representative

Exclusion Criteria:

• Neonates born < 28 and ≥ 37 weeks of gestation
• Neonates with a life expectancy <1 week, which means with very severe critical illness implying foreseeable intercurrent events that could jeopardize the subject's primary outcome assessment including neonates with severe septic shock;
• Neonates requiring or anticipated to undergo extracorporeal membrane oxygenation treatment;
• Neonates with inborn error of metabolism including congenital abnormality of the amino acid metabolism or a family history of such disease;
• Neonates with hyperkalemia > 5.5 mmol/L at inclusion
• Neonates with known severe pathologically elevated plasma concentrations of electrolyte at inclusion including hyperchloridemia > 120 mmol/L;
• Neonates with known severe hyperglycemia >13.9 mmol/L (250 mg/dL) at inclusion;
• Neonates with demonstrated severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia > 4.5 mmol/L (400 mg/dL) at inclusion;
• Neonates with known severe liver failure including plasma ALT (GPT) concentration > 2 times the upper reference limit or conjugated (direct) bilirubin > 34 µmol/L (> 2 mg/dL) at inclusion;
• Neonates with anuria and known severe renal disorder including plasma creatinine concentration > 2 times the upper reference limit at inclusion;
• Neonates with bleeding and severe coagulation disorders including platelet count < 20×109/L at inclusion;
• Neonates with general contraindications to infusion therapy: acute pulmonary edema, overhydration;
• Neonates with known allergy to egg, soy bean or peanut proteins or to any of their active ingredients or excipients;
• Neonates undergoing concomitant treatment with ceftriaxone, even if separate infusion lines are used;
• Neonates undergoing participation in another investigational clinical study at study enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Numeta G13%E; Required PN intake will be determined daily based on clinical condition, calculated nutritional need and enteral nutrition (EN) intake by the attending physician in conjunction with the Investigator. Patients will receive Numeta G13%E until standard of care (SOC) discontinuation of PN, as decided by the attending physician in conjunction with the Investigator for the best interest of the patient or for a maximum of 28 days.	Dietary supplement: Numeta G13%E; Dose selected and dosing schedule are as deemed appropriate by the ordering attending physician in conjunction with the Investigator.
Active Comparator: Compounded Parenteral Nutrition (cPN) solution; Required PN intake will be determined daily based on clinical condition, calculated nutritional need and enteral nutrition (EN) intake by the attending physician in conjunction with the Investigator. Patients will receive cPN until standard of care (SOC) discontinuation of PN, as decided by the attending physician in conjunction with the Investigator for the best interest of the patient or for a maximum of 28 days.	Dietary supplement: Compounded Parenteral Nutrition (cPN) solution; Will be administered as institutional SOC procedure for the hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Weight (SDS or z-score) at Day 14	The change in weight standard deviation score (SDS or z-score) from birth to 14 days of life, calculated according to reference growth chart developed to assess the growth of preterm infants. To be included in the primary endpoint analysis, patients must minimally receive PN up to Day 5.	Baseline (first 24 hours of life) and Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Protein Intake (g/kg/day)	Nutritional intake from PN will be calculated as per any intravenous nutritional intake (Numeta G13%E, cPN and other sources). Nutritional intake from EN (Enteral Nutrition) will be calculated as per label for infant formula and human milk fortifier (HMF). (Protein = amino acids)	Day 1 to 7
Daily Energy Intake (kcal/kg/day)	Nutritional intake from PN will be calculated as per any intravenous nutritional intake (Numeta G13%E, cPN and other sources). Nutritional intake from EN (Enteral Nutrition) will be calculated as per label for infant formula and human milk fortifier (HMF). Energy includes total calories, non-protein calories, glucose calories, lipid calories.	Day 1 to 7
Weekly Protein Intake (g/kg/week)	Nutritional intake from PN will be calculated as per any intravenous nutritional intake (Numeta G13%E, cPN and other sources). Nutritional intake from EN (Enteral Nutrition) will be calculated as per label for infant formula and human milk fortifier (HMF). (Protein = amino acids).	Week 1, Week 2, Week 3, Week 4
Weekly Energy Intake (kcal/kg/week)	Nutritional intake from PN will be calculated as per any intravenous nutritional intake (Numeta G13%E, cPN and other sources). Nutritional intake from EN (Enteral Nutrition) will be calculated as per label for infant formula and human milk fortifier (HMF). Energy includes total calories, non-protein calories, glucose calories, lipid calories.	Week 1, Week 2, Week 3, Week 4
Age (hours) when minimal weight is documented	Measurement=hours.	Day 1
Maximum weight loss (%) from birth weight	Measurement=percentage (%).	Day 1 to Day 14
Time (hours) to regain birth weight	Postnatal age (hours) when body weight is first documented above BW after maximal weight loss.	Day 1 to Day 14
Weight gain velocity up to Day 14	Calculated by taking the difference between the weight at the end of treatment and the minimum weight recorded and dividing it by the total number of treatment days.	Day 1 to Day 14
Change from Baseline in Weight (SDS or z-score) at Day 7, 14, 21 and 28	Standard deviation score (SDS or z-score).	Baseline, Day 7, Day 14, Day 21, Day 28
Change from Baseline in Length (SDS or z-score) at Day 7, 14, 21 and 28	Standard deviation score (SDS or z-score).	Baseline, Day 7, Day 14, Day 21, Day 28
Change from Baseline in Head Circumference (SDS or z-score) at Day 7, 14, 21 and 28	Standard deviation score (SDS or z-score).	Baseline, Day 7, Day 14, Day 21, Day 28
Weekly gain in Weight (g/kg/day) at Day 7, 14, 21 and 28	Measurement=g/kg/day.	Day 7, Day 14, Day 21, Day 28
Weekly gain in Length (cm/week) at Day 7, 14, 21 and 28	Measurement=cm/week.	Day 7, Day 14, Day 21, Day 28
Weekly gain in Head Circumference (cm/week) at Day 7, 14, 21 and 28	Measurement=cm/week.	Day 7, Day 14, Day 21, Day 28
Change from Baseline in Weight (SDS or z-score) at End of study	Measurement=Standard deviation score (SDS or z-score). End of Study=discharge or maximum 40 weeks post-menstrual age.	Baseline up to Week 40
Change from Baseline in Length (SDS or z-score) at End of study	Measurement=Standard deviation score (SDS or z-score).	Baseline up to Week 40
Change from Baseline in Head Circumference (SDS or z-score) at End of study	Measurement=Standard deviation score (SDS or z-score).	Baseline up to Week 40
Gain in Weight (g/kg/week) from Baseline to End of study	Measurement=g/kg/week	Baseline up to Week 40
Gain in Length (cm/week) from Baseline to End of study	Measurement=cm/week.	Baseline up to Week 40
Gain in Head Circumference (cm/week) from Baseline to End of study	Measurement=cm/week.	Baseline up to Week 40
Number of Clinical Characteristics by Type	Including in-hospital deaths, necrotizing enterocolitis (NEC), late onset sepsis (LOS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and cholestasis	Week 1 up to Week 40
Duration of Clinical Characteristics by Type	Including mechanical ventilation duration, PN duration, antibiotic duration, and in-hospital length of stay (LoS)	Week 1 up to Week 40
Adverse Events of special interest (AESIs)		Week 1 up to Week 40

Collaborators and Investigators

• Sponsor: Baxter Healthcare Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): August 20, 2021
• Primary Completion (Estimated): May 30, 2022
• Study Completion (Estimated): May 30, 2022

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: parenteral nutrition
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Infant Nutrition Disorders
• Other Study ID Numbers: BXU512338

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No