Infant,PrematurePhase 4NCT03693287

Personalized vs Standardized PN for Preterm Infants >1250g

A Phase 4 study testing Standardized-parenteral nutrition (S-PN) and Personalized-parenteral nutrition (P-PN) in people with Infant,Premature and Parenteral Nutrition, run by Ospedali Riuniti Ancona at 3 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

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). Read more about this study

Who is it for?: Ages 189 to 258 days
Conditions the study is for: Infant,Premature, Parenteral Nutrition, Growth
What is being tested?: Standardized-parenteral nutrition (S-PN) and Personalized-parenteral nutrition (P-PN)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 150 participants
Where: 3 sitesin 2 countries
Study dates: 4 Jul 2021to 31 Oct 2024
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 189 to 258 days
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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,

Show all 10Show fewer

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 locations and contacts

3 sites in 2 countries.

Virgilio P Carnielli, MD, PhD contact

+39 071 596 2045

v.carnielli@univpm.it

Alessio Correani, MSc, PHD contact

+39 071 596 2888

alessio.correani@gmail.com

Country

City, postcode or hospital

Sites recruiting now only

3 sites in 2 countries

Italy2 sites, 2 recruiting

Ospedali Riuniti Ancona
Ancona, 60123
Virgilio Carnielli, MD, PhD, +390715962045
Recruiting
Azienda Ospedaliera di Padova
Padova
Giovanna Verlato, MD, PhD
Recruiting

Other trials in Italy

Spain1 site, 1 recruiting

Hospital Universitario La Paz
Madrid
Miguel Pipaon, MD, PhD
Recruiting

Other trials in Spain

About this study

Official title: Personalized Versus Standardized Parenteral Nutrition for Preterm Infants With a Birth Weight Greater Than 1250 Grams: a Multicenter Randomized Phase IV Clinical Trial

Read the detailed 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).

Conditions: Infant,Premature, Parenteral Nutrition, Growth
Being tested: Standardized-parenteral nutrition (S-PN), Personalized-parenteral nutrition (P-PN)
Keywords: Preterm, Infant, Parenteral Nutrition, Growth
Medical subject headings: Premature Birth, Hyperphagia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Standardized-parenteral nutrition (S-PN)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).
Personalized-parenteral nutrition (P-PN)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.

Study groups in NCT03693287
Study group	Role	What they receive
Personalized-Parenteral Nutrition (P-PN)	Active comparator	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. Receives: Drug: Personalized-parenteral nutrition (P-PN)
Standardized-Parenteral Nutrition (S-PN)	Experimental	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. Receives: Drug: Standardized-parenteral nutrition (S-PN)

What is being measured

The primary outcome is the main question the study is designed to answer.

WEIGHT CHANGE
Daily weight change (g/kg/d) during parenteral nutrition (PN)
Measured: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). At least 7 days of PN will be required to calculate weight gain during PN.

Secondary outcomes (32)

MUSCLE ULTRASOUND (optional)
Ultrasound measurement of mid thigh and mid arm muscle thickness (cm).
Measured: At the start of PN, after 7, 14 and 28 days (+-1 d).
ADIPOSE TISSUE ULTRASOUND (optional)
Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm).
Measured: At the start of PN, after 7, 14 and 28 days (+-1 d).
BONE ULTRASOUND (optional)
Metacarpus speed of sound (m/s) and metacarpus bone transmission time (ms).
Measured: At the start of PN, after 7, 14 and 28 days (+-1 d).
WEIGHT
Weight measured by a digital infant scale (grams)
Measured: Daily up to 42 weeks of post menstrual age or discharge if it comes first.
TOTAL BODY LENGTH
Total body length measured by a neonatal stadiometer (cm)
Measured: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
HEAD CIRCUMFERENCE
Head circumference measured by a flexible non-stretchable tape (cm)
Measured: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
GLUCIDE TOLERANCE
Blood glycemia (mg/dl).
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
AMINO ACID TOLERANCE
Plasma and urinary urea concentrations (mg/dl).
Measured: At the start of PN, at PN day 7 (+-1 d) and 14 (+-1 d), and then every 2 weeks until the stop of PN (endpoint: PN day 28 if PN duration >28 days).
TRIGLYCERIDE CONCENTRATION
Plasma triglycerides (TG; mg/dl).
Measured: At PN day 3 (+-1 d) and 7(+-1 d), and then every 7 days (+-1 d) until the stop of PN (endpoint: PN day 28 if PN duration >28 days).
FATTY ACID CONCENTRATION (optional)
Plasma fatty acid concentration (FA; mg/dl).
Measured: At PN day 7 (+-1 d).
DICARBOXYLIC AND HYDROXYL FATTY ACID CONCENTRATION (optional)
Urinary dicarboxylic acids (DCA; mmol/mol creatinine) and hydroxyl fatty acids (H-FA; mmol/mol creatinine).
Measured: At PN day 7 (+-1 d).
ELECTROLYTE CONCENTRATION
Hemogasanalysis (Na+, mmol/l; K+, mmol/l; Ca2+, mg/dl; Cl-, mmol/l) and SBE (standard base excess, mmol/L)
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
HYPER AND HYPO-NATREMIA, -KALEMIA, -CHLOREMIA, -PHOSPHATEMIA, -CALCEMIA, AND -PARATHYROIDISM
Episodes of Hyper/Hypo Natremia, -KaIemia, -Chloremia, -Phosphatemia, -Calcemia, and -Parathyroidism (number).
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
METABOLIC ACIDOSIS
SBE < -7.5 mmol/L.
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
BONE MINERALIZATION-1: CALCIUM and PHOSPHORUS CONCENTRATIONS
Plasma and urinary calcium and phosphorus concentrations (mg/dl).
Measured: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
LIVER FUNCTION: ALP, AST, ALT AND GGT CONCENTRATIONS
Plasma alkaline phosphatase (ALP; UI/L), aspartate transaminase (AST; UI/L), alanine transaminase (ALT; UI/L), and gamma-glutamyl transpeptidase (GGT, UI/L).
Measured: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
BONE MINERALIZATION-2: PTH CONCENTRATIONS
Plasma parathormone concentrations (PTH; pg/ml).
Measured: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
BONE MINERALIZATION: PYD, PICP and ICTP CONCENTRATION (optional)
Urinary pyridinoline crosslinks of collagen (Pyd; nmol/L), serum carboxyterminal propeptide of type I procollagen (PICP; ng/mL) and serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP; ng/mL)
Measured: At the start of PN and at PN day 28 (+-1 d) (endpoint).
BILIRUBIN CONCENTRATION
Plasma bilirubin (total and conjugated; mg/dl)
Measured: At PN day 7 (+-1 d). An additional measurement will be performed at PN day 14 (+-1 d) in case of PN duration >14 days.
MORBIDITY - 1
The incidence of the main complication of prematurity (intraventricular hemorrhage of 3° and 4° grade; Periventricular leukomalacia; Patent ductus arteriosus; Retinopathy of Prematurity; Bronchopulmonary dysplasia and Sepsis).
Measured: Up to 42 weeks of post menstrual age or discharge if it comes first.
MORBIDITY - 2
The incidence of Cholestasis and Renal and Hepatic Insufficiency.
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
MORTALITY BEFORE 42 WEEKS POST MENSTRUAL AGE
Death before 42 weeks post menstrual age (number).
Measured: At 42 weeks of post menstrual age or discharge if it comes first.
MORTALITY DURING PARENTERAL NUTRITION
Death during PN (number).
Measured: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
ENTERAL NUTRITION INTAKES
Enteral nutrition intakes (ml/kg).
Measured: Daily from the start of PN to day 28 of life.
PARENTERAL NUTRITION INTAKES: AMINO ACIDS
Intravenous amino acid intakes (g/kg).
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION INTAKES: LIPIDS
Intravenous lipid intakes (g/kg).
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION INTAKES: GLUCOSE
Intravenous glucose intakes (g/kg).
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION DURATION
PN duration (days).
Measured: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
MECHANICAL VENTILATION
Mechanical ventilation duration and oxygen therapy duration (days).
Measured: Up to 42 weeks of post menstrual age or discharge if it comes first.
DRUG THERAPIES
Drug therapy duration (hours).
Measured: Up to 42 weeks of post menstrual age or discharge if it comes first.
PHARMACOECONOMICS
Healthcare costs (euro).
Measured: Up to 42 weeks of post menstrual age or discharge if it comes first.
METABOLIC COMPLICATIONS
Number of hypertriglyceridemic episodes (plasma triglycerides>265mg/dL), hyperglycemic and hypoglycemic episodes (blood glycaemia>175 mg/dL and <40 mg/dL, respectively) and elevated urea (blood urea>100 mg/dL).
Measured: Up to 42 weeks of post menstrual age or discharge if it comes first.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Jul 202131 Oct 2024

First posted2 Oct 2018
Study start4 Jul 2021
Primary completion31 Aug 2023 (estimated)
Study completion31 Oct 2024 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (12)Papers the sponsor has linked to this study.
Other trials for Infant,PrematureStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Participant
Enrolment: 150 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03693287
Sponsor's protocol ID: SP-PP18
Other IDs: 2018-004946-41, 2018
Status last verified: Mar 2023
First submitted: 26 Sep 2018
Last updated: 23 Mar 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 16585322
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.
PubMed 28270894
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.
PubMed 20234142
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.
PubMed 6794364
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.
PubMed 14629529
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.
PubMed 111548
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.
PubMed 25655621
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.
PubMed 8890070
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.
PubMed 11092513
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.
PubMed 3104873
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.
PubMed 3085521
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.
PubMed 7986782

Want to know more?

Virgilio P Carnielli, MD, PhD

+39 071 596 2045

v.carnielli@univpm.it

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Personalized Versus Standardized Parenteral Nutrition for Preterm Infants With a Birth Weight Greater Than 1250 Grams: a Multicenter Randomized Phase IV Clinical Trial
ClinicalTrials.gov ID: NCT03693287
Acronym / sponsor ID: SP-PP18
Conditions: Infant,Premature, Parenteral Nutrition, Growth
Keywords: Preterm, Infant, Parenteral Nutrition, Growth
Phase: Phase 4
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 150 participants (estimated)
Lead sponsor: Ospedali Riuniti AnconaUniversity, hospital or other
Collaborators: Azienda Ospedaliera di Padova, Hospital Universitario La Paz
Study start: 4 Jul 2021 (actual)
Primary completion: 31 Aug 2023 (estimated)
Study completion: 31 Oct 2024 (estimated)
First posted: 2 Oct 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
Personalized-Parenteral Nutrition (P-PN)	Active comparator	Drug: 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.
Standardized-Parenteral Nutrition (S-PN)	Experimental	Drug: 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.

Who may qualify

Ages: 189 to 258 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (10 listed)

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,

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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).	Drug	Standardized-Parenteral Nutrition (S-PN)
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.	Drug	Personalized-Parenteral Nutrition (P-PN)

Primary outcome

WEIGHT CHANGE
Time frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). At least 7 days of PN will be required to calculate weight gain during PN.
Daily weight change (g/kg/d) during parenteral nutrition (PN)

32 secondary outcomes

MUSCLE ULTRASOUND (optional)
Time frame: At the start of PN, after 7, 14 and 28 days (+-1 d).
ADIPOSE TISSUE ULTRASOUND (optional)
Time frame: At the start of PN, after 7, 14 and 28 days (+-1 d).
BONE ULTRASOUND (optional)
Time frame: At the start of PN, after 7, 14 and 28 days (+-1 d).
WEIGHT
Time frame: Daily up to 42 weeks of post menstrual age or discharge if it comes first.
TOTAL BODY LENGTH
Time frame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
HEAD CIRCUMFERENCE
Time frame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
GLUCIDE TOLERANCE
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
AMINO ACID TOLERANCE
Time frame: At the start of PN, at PN day 7 (+-1 d) and 14 (+-1 d), and then every 2 weeks until the stop of PN (endpoint: PN day 28 if PN duration >28 days).
TRIGLYCERIDE CONCENTRATION
Time frame: At PN day 3 (+-1 d) and 7(+-1 d), and then every 7 days (+-1 d) until the stop of PN (endpoint: PN day 28 if PN duration >28 days).
FATTY ACID CONCENTRATION (optional)
Time frame: At PN day 7 (+-1 d).
DICARBOXYLIC AND HYDROXYL FATTY ACID CONCENTRATION (optional)
Time frame: At PN day 7 (+-1 d).
ELECTROLYTE CONCENTRATION
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
HYPER AND HYPO-NATREMIA, -KALEMIA, -CHLOREMIA, -PHOSPHATEMIA, -CALCEMIA, AND -PARATHYROIDISM
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
METABOLIC ACIDOSIS
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
BONE MINERALIZATION-1: CALCIUM and PHOSPHORUS CONCENTRATIONS
Time frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
LIVER FUNCTION: ALP, AST, ALT AND GGT CONCENTRATIONS
Time frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
BONE MINERALIZATION-2: PTH CONCENTRATIONS
Time frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
BONE MINERALIZATION: PYD, PICP and ICTP CONCENTRATION (optional)
Time frame: At the start of PN and at PN day 28 (+-1 d) (endpoint).
BILIRUBIN CONCENTRATION
Time frame: At PN day 7 (+-1 d). An additional measurement will be performed at PN day 14 (+-1 d) in case of PN duration >14 days.
MORBIDITY - 1
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
MORBIDITY - 2
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
MORTALITY BEFORE 42 WEEKS POST MENSTRUAL AGE
Time frame: At 42 weeks of post menstrual age or discharge if it comes first.
MORTALITY DURING PARENTERAL NUTRITION
Time frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
ENTERAL NUTRITION INTAKES
Time frame: Daily from the start of PN to day 28 of life.
PARENTERAL NUTRITION INTAKES: AMINO ACIDS
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION INTAKES: LIPIDS
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION INTAKES: GLUCOSE
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION DURATION
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
MECHANICAL VENTILATION
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
DRUG THERAPIES
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
PHARMACOECONOMICS
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
METABOLIC COMPLICATIONS
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2023.
Background: PubMed 16585322Ehrenkranz 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.
Background: PubMed 28270894Evering 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.
Background: PubMed 20234142Smolkin 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.
Background: PubMed 6794364Dice 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.
Background: PubMed 14629529Yeung 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.
Background: PubMed 111548Mutchie 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.
Background: PubMed 25655621Kreissl 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.
Background: PubMed 8890070Namgung 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.
Background: PubMed 11092513Rossi 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.
Background: PubMed 3104873Jones 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.
Background: PubMed 3085521Schoeller 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.
Background: PubMed 7986782van 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Virgilio P Carnielli, MD, PhD contact

+39 071 596 2045

v.carnielli@univpm.it

Alessio Correani, MSc, PHD contact

+39 071 596 2888

alessio.correani@gmail.com

3 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Virgilio P Carnielli, MD, PhD (+39 071 596 2045, v.carnielli@univpm.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

WEIGHT CHANGE (time frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). At least 7 days of PN will be required to calculate weight gain during PN.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03693287, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2023.