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

Baxter Healthcare Corporation

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Conditions

Eligibility

Sex: ALLMin age: 0 HoursMax age: 24 HoursHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Baseline (first 24 hours of life) and Day 14

Secondary Outcomes

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)

Time frame: Day 1 to 7

Daily Energy Intake (kcal/kg/day)

Time frame: Day 1 to 7

Weekly Protein Intake (g/kg/week)

Time frame: Week 1, Week 2, Week 3, Week 4

Weekly Energy Intake (kcal/kg/week)

Time frame: Week 1, Week 2, Week 3, Week 4

Age (hours) when minimal weight is documented

Measurement=hours.

Time frame: Day 1

Maximum weight loss (%) from birth weight

Measurement=percentage (%).

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: Day 7, Day 14, Day 21, Day 28

Weekly gain in Length (cm/week) at Day 7, 14, 21 and 28

Measurement=cm/week.

Time frame: 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.

Time frame: 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.