Clinical trial NCT03693287: Personalized vs Standardized PN for Preterm Infants >1250g
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Infant,Premature
Parenteral Nutrition
Growth
Keywords: Preterm
Infant
Parenteral Nutrition
Growth
Lead sponsor: Ospedali Riuniti Ancona
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera di Padova
name: Hospital Universitario La Paz
First posted: 2018-10-02
Enrollment: 150
Sex: ALL
Minimum age (years): 189
Maximum age (years): 258
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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 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).

Eligibility criteria: 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.

Primary outcomes:
measure: WEIGHT CHANGE
timeFrame: 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:
measure: MUSCLE ULTRASOUND (optional)
timeFrame: At the start of PN, after 7, 14 and 28 days (+-1 d).
measure: ADIPOSE TISSUE ULTRASOUND (optional)
timeFrame: At the start of PN, after 7, 14 and 28 days (+-1 d).
measure: BONE ULTRASOUND (optional)
timeFrame: At the start of PN, after 7, 14 and 28 days (+-1 d).
measure: WEIGHT
timeFrame: Daily up to 42 weeks of post menstrual age or discharge if it comes first.
measure: TOTAL BODY LENGTH
timeFrame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
measure: HEAD CIRCUMFERENCE
timeFrame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
measure: GLUCIDE TOLERANCE
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: AMINO ACID TOLERANCE
timeFrame: 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).
measure: TRIGLYCERIDE CONCENTRATION
timeFrame: 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).
measure: FATTY ACID CONCENTRATION (optional)
timeFrame: At PN day 7 (+-1 d).
measure: DICARBOXYLIC AND HYDROXYL FATTY ACID CONCENTRATION (optional)
timeFrame: At PN day 7 (+-1 d).
measure: ELECTROLYTE CONCENTRATION
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: HYPER AND HYPO-NATREMIA, -KALEMIA, -CHLOREMIA, -PHOSPHATEMIA, -CALCEMIA, AND -PARATHYROIDISM
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: METABOLIC ACIDOSIS
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: BONE MINERALIZATION-1: CALCIUM and PHOSPHORUS CONCENTRATIONS
timeFrame: 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.
measure: LIVER FUNCTION: ALP, AST, ALT AND GGT CONCENTRATIONS
timeFrame: 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.
measure: BONE MINERALIZATION-2: PTH CONCENTRATIONS
timeFrame: 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.
measure: BONE MINERALIZATION: PYD, PICP and ICTP CONCENTRATION (optional)
timeFrame: At the start of PN and at PN day 28 (+-1 d) (endpoint).
measure: BILIRUBIN CONCENTRATION
timeFrame: 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.
measure: MORBIDITY - 1
timeFrame: Up to 42 weeks of post menstrual age or discharge if it comes first.
measure: MORBIDITY - 2
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: MORTALITY BEFORE 42 WEEKS POST MENSTRUAL AGE
timeFrame: At 42 weeks of post menstrual age or discharge if it comes first.
measure: MORTALITY DURING PARENTERAL NUTRITION
timeFrame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: ENTERAL NUTRITION INTAKES
timeFrame: Daily from the start of PN to day 28 of life.
measure: PARENTERAL NUTRITION INTAKES: AMINO ACIDS
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: PARENTERAL NUTRITION INTAKES: LIPIDS
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: PARENTERAL NUTRITION INTAKES: GLUCOSE
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: PARENTERAL NUTRITION DURATION
timeFrame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
measure: MECHANICAL VENTILATION
timeFrame: Up to 42 weeks of post menstrual age or discharge if it comes first.
measure: DRUG THERAPIES
timeFrame: Up to 42 weeks of post menstrual age or discharge if it comes first.
measure: PHARMACOECONOMICS
timeFrame: Up to 42 weeks of post menstrual age or discharge if it comes first.
measure: METABOLIC COMPLICATIONS
timeFrame: Up to 42 weeks of post menstrual age or discharge if it comes first.
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Ospedali Riuniti Ancona
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
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