Personalized vs Standardized PN for Preterm Infants >1250g

Ospedali Riuniti Ancona

Status and phase: Enrolling; Phase 4

Conditions: Infant,Premature; Parenteral Nutrition; Growth

Treatments: Drug: Personalized-parenteral nutrition (P-PN); Drug: Standardized-parenteral nutrition (S-PN)

Study type: Interventional

Funder types: Other

Identifiers

NCT03693287

2018-004946-41 (EudraCT Number)

SP-PP18

Details and patient eligibility

About

Preterm infants (gestational age between 189 and 258 days) with a birth weight (BW) greater than 1250 grams will be randomized to personalized-parenteral nutrition (P-PN) or standardized-parenteral nutrition (S-PN). The aim of the study is to evaluate the effect of S-PN versus P-PN on growth of preterm infants with BW>1250 grams.

Full description

Parenteral nutrition (PN) is a crucial part of the clinical care of preterm infants. Traditionally different components of PN are prescribed individually considering requirements of an individual infant (P-PN). Recently, standardized PN formulations (S-PN) for preterm infants have been assessed and may have advantages including a better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bags that provides total nutrient admixture for infants may have the additional advantage of decreased risk of contamination and ease of administration.

The proposed intervention and hypothesis: The investigators propose a multi-centered Phase IV RCT to compare S-PN versus P-PN, that is the usual care for preterm infants with a birth weight >1250 grams requiring PN in the intensive care units involved in the study. The investigators hypothesize that weight gain during PN of preterm infants with a BW greater than 1250 grams who received S-PN is not statically inferior (< 2g/kg/d) to that of infants who received P-PN (Non-inferiority study).

Study design: Preterm infants (gestational age between 189 and 258 days) with a BW greater than 1250 grams will be enrolled during hospitalization after the informed consent is drawn from parents or legal guardians. All infants will undergo a physical examination and the need of PN will be judged by the caring physician according to predefined criteria. Infants requiring PN will be divided into 3 clinical groups:

• Group A or EARLY HIGH-RISK INFANTS: these infants present in rather severe conditions at birth or soon after birth which make enteral nutrition (EN) impossible or non-desirable. In this group of infants, the investigators will include patients with Perinatal asphyxia, Perinatal shock (Cardiovascular or Septic), GI malformations, Severe Intra-uterine growth retardation (IUGR) with markedly abnormal prenatal doppler, and Miscellanea. These infants will have a central venous access soon after birth.
• Group B or INSUFFICIENT EN INTAKE: these Infants are in rather stable conditions after birth, however these infants may exhibit gastrointestinal (GI) intolerance of any origin. These patients will be randomized after 72 hours of life if the mean EN volume of the first 72-hrs of life will be less than 30 ml/kg/d or if EN intake on the third day will be less than 45 ml/kg/d. In this category, the investigators will include also those infants who will have their EN intake reduced below 30 ml/kg for 3 consecutive days (usually from day 3 through day 6) because of PDA treatment. These infants will have a central venous access inserted on the 3rd or 4th day of life if not already in place.
• Group C or LATE SICKNESS: these are the infants that experience a major sickness after a variable period of good gastrointestinal tolerance. In this group, the investigators will have infants with Necrotizing Enterocolitis (NEC), Severe Sepsis with abdominal distension and poor peristalsis, Septic Shock, or other severe unexpected conditions such as volvulus etc. These infants will also have a central venous access.

Study infants within each clinical group will be divided into 2 blocks on the basis of their BW: 1250-1750 g (Block A) e >1750 g (Block B). Infants of each study group will be then randomly assigned to P-PN or S-PN (Intervention-arm). The study PN bags will be used until the study infants will not be able to tolerate 135 ml/kg/d enterally (range: 120-160 ml/kg/d according to the local practice) or until day 28 of PN (after the 28th day of PN, patients will receive PN according to the normal clinical practice).

Enrollment: 150 estimated patients

Sex: All

Ages: 189 to 258 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Birth weight greater than 1250 grams,
• Gestational age between 189 and 258 days,
• In need of parenteral nutrition (PN),
• Signed informed consent by at least one parent or legal guardian.

Exclusion criteria

• Genetic, metabolic, or endocrine disorders diagnosed before/after enrolment
• Ceftriaxone or Coumarin therapy before/after enrolment,
• Calcium therapy before enrolment,
• Cholestasis or hepatic insufficiency before enrolment,
• Renal insufficiency before enrolment,
• Hyponatremia before enrolment,
• Hypertriglyceridemia before enrolment,
• Hypersensitivity reaction to components of parenteral nutrition before/after enrolment,
• Off-label use of drug therapy before/after enrolment,
• Absent informed consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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150 participants in 2 patient groups

Personalized-Parenteral Nutrition (P-PN)

Active Comparator group

Description:

These patients will receive personalized parenteral nutrition (PN) as it is customary in the participating centers. Dosing range: glucose from 9 to 13 g/kg/d, AA from 2.0 to 3.0 g/kg/d, and FAT from 1.5 to 2.5 g/kg/d. Intravenous macronutrient intakes: * PN day 1: 2.0 g/kg of AA, 1.6 g/kg of FAT and 9 g/kg of glucides. * PN day 2: 2.5 g/kg of AA, 2.0 g/kg of FAT and 11 g/kg of glucides. * PN day 3 and the days after: 3.0 g/kg of AA, 2.5 g/kg of FAT and 13 g/kg of glucides. Intravenous vitamins will be supplied according to local clinical practice. Variations in macronutrient intakes will be tolerated within ±20%. Nutritional goal: to ensure at least 2.5 g/kg/d of AA and 70 kcal/kg/d of no protein energy (NPE) from PN day 2.

Treatment:

Drug: Personalized-parenteral nutrition (P-PN)

Standardized-Parenteral Nutrition (S-PN)

Experimental group

Description:

These patients will receive standardized parenteral nutrition (PN) by using a triple chamber bag (Numeta G13%E®). Dosing range: 80-300 ml/d. Intravenous macronutrient intakes: 65 ml/kg at PN day 1, 80 ml/kg at PN day 2 and then 100 ml/kg from PN day 3. Nutritional goal: to ensure at least 2.5 g/kg/d of amino acids (AA) and 70 kcal/kg/d of no protein energy (NPE) from PN day 2.

Treatment:

Drug: Standardized-parenteral nutrition (S-PN)