Personalized vs Standardized PN for Preterm Infants >1250g

Sponsor:

Collaborators:

Information provided by (Responsible Party):

Virgilio Paolo Carnielli，Università Politecnica delle Marche

Tracking Information

First Submitted Date ^ICMJE

September 26, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 2, 2018

Actual Study Start Date ^ICMJE

November 1, 2018

Estimated Primary Completion Date

April 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

WEIGHT CHANGE[ Time Frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). At least 5 days of PN will be required to calculate weight gain. ]

Daily weight change (g/kg/d) during parenteral nutrition (PN)

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

LEAN BODY MASS (optional)[ Time Frame: At the stop of PN (+-1 d) if PN duration ≥ 7 days. ]
Lean body mass will be measured by the deuterium dilution method. Urinary deuterium enrichment after 6 and 12 hours from deuterium oral administration (baseline).
MUSCLE ULTRASOUND (optional)[ Time Frame: At the start of PN, after 28 days (+-1 d) from the start of PN and at 252 days (+-1 d) of post menstrual age. Measurements will be performed every 7 days (+-1 d) from the start of PN to 252 days (+-1 d) of post menstrual age if it is possible. ]
Ultrasound measurement of mid thigh and mid arm muscle thickness (cm).
ADIPOSE TISSUE ULTRASOUND (optional)[ Time Frame: At the start of PN, after 28 days (+-1 d) from the start of PN and at 252 days (+-1 d) of post menstrual age. Measurements will be performed every 7 days (+-1 d) from the start of PN to 252 days (+-1 d) of post menstrual age if it is possible. ]
Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm).
BONE ULTRASOUND (optional)[ Time Frame: At the start of PN, after 28 days (+-1 d) from the start of PN and at 252 days (+-1 d) of post menstrual age. Measurements will be performed every 7 days (+-1 d) from the start of PN to 252 days (+-1 d) of post menstrual age if it is possible. ]
Metacarpus speed of sound (m/s) and metacarpus bone transmission time (ms).
WEIGHT[ Time Frame: Daily up to 42 weeks of post menstrual age. ]
Weight measured by a digital infant scale (grams)
TOTAL BODY LENGTH[ Time Frame: Weekly up to 42 weeks of post menstrual age. ]
Total body length measured by a neonatal stadiometer (cm)
HEAD CIRCUMFERENCE[ Time Frame: Weekly up to 42 weeks of post menstrual age. ]
Head circumference measured by a flexible non-stretchable tape (cm)
GLUCIDE TOLERANCE[ Time Frame: Daily until PN day 7. ]
Blood glycemia (mg/dl).
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). ]
Plasma and urinary urea concentrations (mg/dl).
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). ]
Plasma triglycerides (TG; mg/dl).
FATTY ACID CONCENTRATION (optional)[ Time Frame: At PN day 7 (+-1 d). ]
Plasma fatty acid concentration (FA; mg/dl).
DICARBOXYLIC AND HYDROXYL FATTY ACID CONCENTRATION (optional)[ Time Frame: At PN day 7 (+-1 d). ]
Urinary dicarboxylic acids (DCA; mmol/mol creatinine) and hydroxyl fatty acids (H-FA; mmol/mol creatinine).
ELECTROLYTE CONCENTRATION[ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
Hemogasanalysis (Na+, mmol/l; K+, mmol/l; Ca2+, mg/dl; Cl-, mmol/l).
HYPER AND HYPO-NATREMIA AND -KALIEMIA[ Time Frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
Episodes of Hyper/Hypo Natremia (number) and Hyper/Hypo Kaliemia (number).
BONE MINERALIZATION: CALCIUM, PHOSPHORUS, ALP and PTH CONCENTRATION[ 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 (PN duration ≥28 days). ]
Plasma calcium and phosphorus (mg/dl), alkaline phosphatase (ALP; UI/L), parathormone (PTH; pg/ml), urinary calcium and phosphorus (mg/dl).
BONE MINERALIZATION: PYD, PICP and ICTP CONCENTRATION (optional)[ Time Frame: At the start of PN and at PN day 28 (+-1 d) (endpoint). Additional measurements will be performed before and/or after the predefined endpoint if it is possible. ]
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)
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. ]
Plasma bilirubin (total and conjugated; mg/dl)
MORBIDITY[ Time Frame: Up to 42 weeks of post menstrual age. ]
Incidence of the main complication of prematurity (intraventricular hemorrhage of 3° and 4° grade; Periventricular leukomalacia; Patent ductus arteriosus; Retinopathy of Prematurity; Bronchopulmonary dysplasia; Sepsis).
MORTALITY BEFORE 42 WEEKS POST MENSTRUAL AGE[ Time Frame: At 42 weeks of post menstrual age. ]
Death before 42 weeks post menstrual age (number).
MORTALITY DURING PN[ Time Frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
Death during PN (number).
INTERVENTIONS-1[ Time Frame: Up to 42 weeks of post menstrual age. ]
Duration of selected interventions: PN and mechanical ventilation (days).
PHARMACOECONOMICS[ Time Frame: Up to 42 weeks of post menstrual age. ]
Healthcare costs (euro).

Descriptive Information

Brief Title ^ICMJE

Personalized vs Standardized PN for Preterm Infants >1250g

Official Title ^ICMJE

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

Brief Summary

Preterm infants (gestational age <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

Parenteral nutrition (PN) is a crucial part of 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 better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bag 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 III 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 of preterm infants with a BW greater than 1250 grams who received S-PN is not statically inferior (< 1g/kg/d) to that of infants who received P-PN (Non-inferiority study). Study design: Preterm infants (gestational age < 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 in 3 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). PN will be administered to study infants until these infants will not be able to tolerate 135 ml/kg/d enterally (range: 120-150 ml/kg/d according to the local practice).

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: Numeta G13®, BAXTER Spa
NUMETA G13 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 gestation age).
Drug: Personalized-parenteral nutrition.
Glucose will preferably be "dextrose 50%", amino acids (AA) will be "Primene®, BAXTER Spa" and lipids (FAT) will be "Clinoleic®, BAXTER Spa". Electrolytes and vitamins will be Soluvit® or Vitalipid®, FRESENIUS KABI Spa. Parenteral nutrition bags will be prepared by the hospital pharmacy according to the prescription of the attending neonatologist.

Study Arms

Active Comparator: 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. Duration of treatment: maximum 28 days
Experimental: Standardized-Parenteral Nutrition (S-PN)
These patients will receive standardized parenteral nutrition (PN) by using a triple chamber bag (Numeta G13®, BAXTER Spa). 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. Duration of treatment: maximum 28 days.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

150

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

May 30, 2021

Estimated Primary Completion Date

April 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: - birth weight greater than 1250 grams - gestational age lower than 258 days - in need of parenteral nutrition (PN) - informed consent form signed by at least one parent or legal guardian Exclusion Criteria: - high likelihood of death in the next 7 days from the start of PN - genetic, metabolic, or endocrine disorders diagnosed before enrolment - withdrawal of informed consent.

Sex/Gender

Sexes Eligible for Study:

All

Ages

168 Days and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

Virgilio Paolo Carnielli，Università Politecnica delle Marche

Study Sponsor ^ICMJE

Università Politecnica delle Marche

Collaborators ^ICMJE

Investigators ^ICMJE

PRS Account

Università Politecnica delle Marche

Verification Date

September 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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