Personalized vs Standardized PN for Preterm Infants >1250g

NCT ID: NCT03693287

Last Updated: 2023-03-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-04

Study Completion Date

2024-10-31

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Infant,Premature Parenteral Nutrition Growth

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants
Patients/Parents/Legal guardian will be masked. The statistician will be also masked when analyzing the data.

Study Groups

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Personalized-Parenteral Nutrition (P-PN)

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.

Group Type ACTIVE_COMPARATOR

Personalized-parenteral nutrition (P-PN)

Intervention Type DRUG

Intravenous glucose will be "dextrose 50%", amino acids (AA) will be "Primene®" and lipids (FAT) will be "Clinoleic®".

Parenteral nutrition bags will be prepared by the hospital pharmacy according to the prescription of the attending neonatologist.

Standardized-Parenteral Nutrition (S-PN)

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.

Group Type EXPERIMENTAL

Standardized-parenteral nutrition (S-PN)

Intervention Type DRUG

NUMETA G13%E 300 mL is a triple-chamber (lipid emulsion, amino acids solution with electrolytes, and glucose solution), ready-to-use parenteral nutrition product available to treat preterm infants (less than 37 weeks gestational age).

Interventions

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Standardized-parenteral nutrition (S-PN)

NUMETA G13%E 300 mL is a triple-chamber (lipid emulsion, amino acids solution with electrolytes, and glucose solution), ready-to-use parenteral nutrition product available to treat preterm infants (less than 37 weeks gestational age).

Intervention Type DRUG

Personalized-parenteral nutrition (P-PN)

Intravenous glucose will be "dextrose 50%", amino acids (AA) will be "Primene®" and lipids (FAT) will be "Clinoleic®".

Parenteral nutrition bags will be prepared by the hospital pharmacy according to the prescription of the attending neonatologist.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

189 Days

Maximum Eligible Age

258 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Ospedaliera di Padova

OTHER

Sponsor Role collaborator

Hospital Universitario La Paz

OTHER

Sponsor Role collaborator

Ospedali Riuniti Ancona

OTHER

Sponsor Role lead

Responsible Party

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Virgilio Paolo Carnielli

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Ospedali Riuniti Ancona

Ancona, , Italy

Site Status RECRUITING

Azienda Ospedaliera di Padova

Padua, , Italy

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Countries

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Italy Spain

Central Contacts

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Virgilio P Carnielli, MD, PhD

Role: CONTACT

+39 071 596 2045

Alessio Correani, MSc, PHD

Role: CONTACT

+39 071 596 2888

Facility Contacts

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Virgilio Carnielli, MD, PhD

Role: primary

+390715962045

Giovanna Verlato, MD, PhD

Role: primary

Miguel Pipaon, MD, PhD

Role: primary

References

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Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics. 2006 Apr;117(4):1253-61. doi: 10.1542/peds.2005-1368.

Reference Type BACKGROUND
PMID: 16585322 (View on PubMed)

Evering VH, Andriessen P, Duijsters CE, Brogtrop J, Derijks LJ. The Effect of Individualized Versus Standardized Parenteral Nutrition on Body Weight in Very Preterm Infants. J Clin Med Res. 2017 Apr;9(4):339-344. doi: 10.14740/jocmr2893w. Epub 2017 Feb 21.

Reference Type BACKGROUND
PMID: 28270894 (View on PubMed)

Smolkin T, Diab G, Shohat I, Jubran H, Blazer S, Rozen GS, Makhoul IR. Standardized versus individualized parenteral nutrition in very low birth weight infants: a comparative study. Neonatology. 2010;98(2):170-8. doi: 10.1159/000282174. Epub 2010 Mar 16.

Reference Type BACKGROUND
PMID: 20234142 (View on PubMed)

Dice JE, Burckart GJ, Woo JT, Helms RA. Standardized versus pharmacist-monitored individualized parenteral nutrition in low-birth-weight infants. Am J Hosp Pharm. 1981 Oct;38(10):1487-9.

Reference Type BACKGROUND
PMID: 6794364 (View on PubMed)

Yeung MY, Smyth JP, Maheshwari R, Shah S. Evaluation of standardized versus individualized total parenteral nutrition regime for neonates less than 33 weeks gestation. J Paediatr Child Health. 2003 Nov;39(8):613-7. doi: 10.1046/j.1440-1754.2003.00246.x.

Reference Type BACKGROUND
PMID: 14629529 (View on PubMed)

Mutchie KD, Smith KA, MacKay MW, Marsh C, Juluson D. Pharmacist monitoring of parenteral nutrition: clinical and cost effectiveness. Am J Hosp Pharm. 1979 Jun;36(6):785-7.

Reference Type BACKGROUND
PMID: 111548 (View on PubMed)

Kreissl A, Repa A, Binder C, Thanhaeuser M, Jilma B, Berger A, Haiden N. Clinical Experience With Numeta in Preterm Infants: Impact on Nutrient Intake and Costs. JPEN J Parenter Enteral Nutr. 2016 May;40(4):536-42. doi: 10.1177/0148607115569733. Epub 2015 Feb 5.

Reference Type BACKGROUND
PMID: 25655621 (View on PubMed)

Namgung R, Tsang RC, Sierra RI, Ho ML. Normal serum indices of bone collagen biosynthesis and degradation in small for gestational age infants. J Pediatr Gastroenterol Nutr. 1996 Oct;23(3):224-8. doi: 10.1097/00005176-199610000-00004.

Reference Type BACKGROUND
PMID: 8890070 (View on PubMed)

Rossi L, Branca F, Cianfarani S. Collagen cross-links and early postnatal growth in newborns with intrauterine growth retardation. Metabolism. 2000 Nov;49(11):1467-72. doi: 10.1053/meta.2000.17670.

Reference Type BACKGROUND
PMID: 11092513 (View on PubMed)

Jones PJ, Winthrop AL, Schoeller DA, Swyer PR, Smith J, Filler RM, Heim T. Validation of doubly labeled water for assessing energy expenditure in infants. Pediatr Res. 1987 Mar;21(3):242-6. doi: 10.1203/00006450-198703000-00007.

Reference Type BACKGROUND
PMID: 3104873 (View on PubMed)

Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Baertschi P, Jequier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol. 1986 May;250(5 Pt 2):R823-30. doi: 10.1152/ajpregu.1986.250.5.R823.

Reference Type BACKGROUND
PMID: 3085521 (View on PubMed)

van Marken Lichtenbelt WD, Westerterp KR, Wouters L. Deuterium dilution as a method for determining total body water: effect of test protocol and sampling time. Br J Nutr. 1994 Oct;72(4):491-7. doi: 10.1079/bjn19940053.

Reference Type BACKGROUND
PMID: 7986782 (View on PubMed)

Other Identifiers

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2018-004946-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SP-PP18

Identifier Type: -

Identifier Source: org_study_id

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